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Behavioral Methods Used in the Study of Learning and Memory

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Drug Discovery and Evaluation: Pharmacological Assays

Abstract

The methods associated with the study of learning and memory functions are vast. Our understanding of the neural mechanisms underlying learning is new and evolving, at least in comparison to many of the techniques and basic principles of learning, which have been known for some time and have been summarized in some detail (Gallistel 1990; Mackintosh 1974). This chapter will discuss the major techniques currently being used in the main species used to study learning and memory in animal models, concentrating on techniques in mice and rats. Where appropriate, discussion of methods in other species will be considered with respect to particular methods, as well as some general discussion of other species used in learning and memory research. The goal of this chapter will primarily be to characterize the behavioral methods that are used to study learning and memory functions in behavioral pharmacology, behavioral neuroscience, and behavioral genetics. These techniques are used in basic science studies as well as in pharmaceutical drug development. Secondarily, methods will be described that induce various types of impairments in learning and memory function, as these are commonly used to understand those conditions and to develop drugs that may improve learning and memory function. These methods include both treatments that produce impairments of learning and memory function, as well as models of genetic conditions that alter these functions.

With contributions by F. J. Hock, F. P. Huger, W. H. Vogel, J. D. Brioni, J. L. McGaugh, and E. Dere from previous editions of this volume.

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References and Further Reading

Introduction

  • Campbell BA, Spear NE (1972) Ontogeny of memory. Psychol Rev 79:215–236

    CAS  PubMed  Google Scholar 

  • Foster TC (1999) Involvement of hippocampal synaptic plasticity in age-related memory decline. Brain Res Brain Res Rev 30:236–249

    CAS  PubMed  Google Scholar 

  • Gallagher M, Pelleymounter MA (1988) Spatial learning deficits in old rats: a model for memory decline in the aged. Neurobiol Aging 9:549–556

    CAS  PubMed  Google Scholar 

  • Gallistel CR (1990) The organization of learning. MIT Press, Cambridge, MA

    Google Scholar 

  • Henry JD, Phillips LH, Crawford JR, Kliegel M, Theodorou G, Summers F (2007) Traumatic brain injury and prospective memory: influence of task complexity. J Clin Exp Neuropsychol 29:457–466

    PubMed  Google Scholar 

  • King EC, Pattwell SS, Glatt CE, Lee FS (2014) Sensitive periods in fear learning and memory. Stress 17:13–21

    PubMed Central  CAS  PubMed  Google Scholar 

  • Mackintosh NJ (1974) The psychology of animal learning. Academic, London/New York

    Google Scholar 

  • McKone E, Crookes K, Jeffery L, Dilks DD (2012) A critical review of the development of face recognition: experience is less important than previously believed. Cogn Neuropsychol 29:174–212

    PubMed  Google Scholar 

  • Myslivecek J (1997) Inhibitory learning and memory in newborn rats. Prog Neurobiol 53:399–430

    CAS  PubMed  Google Scholar 

  • Pedersen NL, Gerritsen L (2015) Genetics of brain and cognitive aging: introduction to the special issue of neuropsychology review. Neuropsychol Rev 25:1–2

    PubMed  Google Scholar 

  • Rice DC (1987) Primate research: relevance to human learning and development. Dev Pharmacol Ther 10:314–327

    CAS  PubMed  Google Scholar 

  • Spear NE, Campbell BA (1979) Ontogeny of learning and memory. L. Erlbaum Associates, Hillsdale, NJ, USA

    Google Scholar 

  • Sweatt JD (2009) Experience-dependent epigenetic modifications in the central nervous system. Biol Psychiatry 65:191–197

    PubMed Central  PubMed  Google Scholar 

  • van Praag H, Kempermann G, Gage FH (2000) Neural consequences of environmental enrichment. Nat Rev Neurosci 1:191–198

    PubMed  Google Scholar 

  • Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014) Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 5:88

    PubMed Central  PubMed  Google Scholar 

Classical Conditioning

  • Mackintosh NJ (1974) The psychology of animal learning. Academic, London/New York

    Google Scholar 

  • Pavlov IP, Anrep GV (1927) Conditioned reflexes; an investigation of the physiological activity of the cerebral cortex. Oxford University Press, London

    Google Scholar 

Fear Conditioning

  • Bernardi RE, Spanagel R (2014) Enhanced extinction of contextual fear conditioning in ClockDelta19 mutant mice. Behav Neurosci 128:468–473

    PubMed  Google Scholar 

  • Chen LS, Tzeng WY, Chuang JY, Cherng CG, Gean PW, Yu L (2014) Roles of testosterone and amygdaloid LTP induction in determining sex differences in fear memory magnitude. Horm Behav 66:498–508

    CAS  PubMed  Google Scholar 

  • Czerniawski J, Ree F, Chia C, Otto T (2012) Dorsal versus ventral hippocampal contributions to trace and contextual conditioning: differential effects of regionally selective NMDA receptor antagonism on acquisition and expression. Hippocampus 22:1528–1539

    PubMed  Google Scholar 

  • Dalla C, Shors TJ (2009) Sex differences in learning processes of classical and operant conditioning. Physiol Behav 97:229–238

    PubMed Central  CAS  PubMed  Google Scholar 

  • Diamantopoulou A, Oitzl MS, Grauer E (2012) Fear memory for cue and context: opposite and time-dependent effects of a physiological dose of corticosterone in male BALB/c and C57BL/6J mice. Brain Res 1466:112–118

    CAS  PubMed  Google Scholar 

  • Drew MR, Denny CA, Hen R (2010) Arrest of adult hippocampal neurogenesis in mice impairs single- but not multiple-trial contextual fear conditioning. Behav Neurosci 124:446–454

    PubMed Central  PubMed  Google Scholar 

  • Dubroqua S, Low SR, Yee BK, Singer P (2015) Caffeine impairs the acquisition and retention, but not the consolidation of Pavlovian conditioned freezing in mice. Psychopharmacology (Berl) 232:721–731

    CAS  Google Scholar 

  • Kim JJ, Jung MW (2006) Neural circuits and mechanisms involved in Pavlovian fear conditioning: a critical review. Neurosci Biobehav Rev 30:188–202

    PubMed Central  PubMed  Google Scholar 

  • Kwon JT, Nakajima R, Kim HS, Jeong Y, Augustine GJ, Han JH (2014) Optogenetic activation of presynaptic inputs in lateral amygdala forms associative fear memory. Learn Mem 21:627–633

    PubMed Central  PubMed  Google Scholar 

  • March A, Borchelt D, Golde T, Janus C (2014) Differences in memory development among C57BL/6NCrl, 129S2/SvPasCrl, and FVB/NCrl mice after delay and trace fear conditioning. Comp Med 64:4–12

    PubMed Central  CAS  PubMed  Google Scholar 

  • Schaap MW, van Oostrom H, Doornenbal A, van ’t Klooster J, Baars AM, Arndt SS, Hellebrekers LJ (2013) Nociception and conditioned fear in rats: strains matter. PLoS One 8:e83339

    PubMed Central  PubMed  Google Scholar 

  • Shechner T, Hong M, Britton JC, Pine DS, Fox NA (2014) Fear conditioning and extinction across development: evidence from human studies and animal models. Biol Psychol 100:1–12

    PubMed Central  PubMed  Google Scholar 

  • Skorzewska A, Lehner M, Wislowska-Stanek A, Turzynska D, Sobolewska A, Krzascik P, Plaznik A (2015) Midazolam treatment before re-exposure to contextual fear reduces freezing behavior and amygdala activity differentially in high- and low-anxiety rats. Pharmacol Biochem Behav 129:34–44

    CAS  PubMed  Google Scholar 

  • Soya S, Shoji H, Hasegawa E, Hondo M, Miyakawa T, Yanagisawa M, Mieda M, Sakurai T (2013) Orexin receptor-1 in the locus coeruleus plays an important role in cue-dependent fear memory consolidation. J Neurosci 33:14549–14557

    CAS  PubMed  Google Scholar 

  • Vouimba RM, Maroun M (2011) Learning-induced changes in mPFC-BLA connections after fear conditioning, extinction, and reinstatement of fear. Neuropsychopharmacol 36:2276–2285

    CAS  Google Scholar 

  • Yamada D, Zushida K, Wada K, Sekiguchi M (2009) Pharmacological discrimination of extinction and reconsolidation of contextual fear memory by a potentiator of AMPA receptors. Neuropsychopharmacol 34:2574–2584

    CAS  Google Scholar 

Fear Potentiated Startle

  • Burman MA, Hamilton KL, Gewirtz JC (2010) Role of corticosterone in trace and delay conditioned fear-potentiated startle in rats. Behav Neurosci 124:294–299

    PubMed Central  CAS  PubMed  Google Scholar 

  • Daldrup T, Remmes J, Lesting J, Gaburro S, Fendt M, Meuth P, Kloke V, Pape HC, Seidenbecher T (2015) Expression of freezing and fear-potentiated startle during sustained fear in mice. Genes Brain Behav 14:281–291

    CAS  PubMed  Google Scholar 

  • Dalla C, Shors TJ (2009) Sex differences in learning processes of classical and operant conditioning. Physiol Behav 97:229–238

    PubMed Central  CAS  PubMed  Google Scholar 

  • Davis M (1990) Pharmacological and anatomical analysis of fear conditioning. NIDA Res Monogr 97:126–162

    CAS  PubMed  Google Scholar 

  • Jones SV, Heldt SA, Davis M, Ressler KJ (2005) Olfactory-mediated fear conditioning in mice: simultaneous measurements of fear-potentiated startle and freezing. Behav Neurosci 119:329–335

    PubMed Central  PubMed  Google Scholar 

  • Koch M (1999) The neurobiology of startle. Prog Neurobiol 59:107–128

    CAS  PubMed  Google Scholar 

  • Lehmann H, Sparks FT, O’Brien J, McDonald RJ, Sutherland RJ (2010) Retrograde amnesia for fear-potentiated startle in rats after complete, but not partial, hippocampal damage. Neuroscience 167:974–984

    CAS  PubMed  Google Scholar 

  • Lissek S, van Meurs B (2014) Learning models of PTSD: theoretical accounts and psychobiological evidence. Int J Psychophysiol, http://dx.doi.org/10.1016/j.ijpsycho.2014.11.006

  • Pardon MC, Gould GG, Garcia A, Phillips L, Cook MC, Miller SA, Mason PA, Morilak DA (2002) Stress reactivity of the brain noradrenergic system in three rat strains differing in their neuroendocrine and behavioral responses to stress: implications for susceptibility to stress-related neuropsychiatric disorders. Neuroscience 115:229–242

    CAS  PubMed  Google Scholar 

  • Pare D, Quirk GJ, Ledoux JE (2004) New vistas on amygdala networks in conditioned fear. J Neurophysiol 92:1–9

    PubMed  Google Scholar 

  • Powers MS, Barrenha GD, Mlinac NS, Barker EL, Chester JA (2010) Effects of the novel endocannabinoid uptake inhibitor, LY2183240, on fear-potentiated startle and alcohol-seeking behaviors in mice selectively bred for high alcohol preference. Psychopharmacology (Berl) 212:571–583

    CAS  Google Scholar 

  • Schwienbacher I, Schnitzler HU, Westbrook RF, Richardson R, Fendt M (2006) Carbachol injections into the nucleus accumbens disrupt acquisition and expression of fear-potentiated startle and freezing in rats. Neuroscience 140:769–778

    CAS  PubMed  Google Scholar 

  • Smith KS, Meloni EG, Myers KM, Van’t Veer A, Carlezon WA Jr, Rudolph U (2011) Reduction of fear-potentiated startle by benzodiazepines in C57BL/6J mice. Psychopharmacology (Berl) 213:697–706

    CAS  Google Scholar 

  • Trivedi MA, Coover GD (2006) Neurotoxic lesions of the dorsal and ventral hippocampus impair acquisition and expression of trace-conditioned fear-potentiated startle in rats. Behav Brain Res 168:289–298

    PubMed  Google Scholar 

  • Yap CS, Richardson R (2007) The ontogeny of fear-potentiated startle: effects of earlier-acquired fear memories. Behav Neurosci 121:1053–1062

    PubMed  Google Scholar 

Eye Blink Conditioning

  • Carretero-Guillen A, Pacheco-Calderon R, Delgado-Garcia JM, Gruart A (2013) Involvement of hippocampal inputs and intrinsic circuit in the acquisition of context and cues during classical conditioning in behaving rabbits. Cereb Cortex

    Google Scholar 

  • Cooke SF, Attwell PJ, Yeo CH (2004) Temporal properties of cerebellar-dependent memory consolidation. J Neurosci 24:2934–2941

    CAS  PubMed  Google Scholar 

  • el-Zahaby HM, Ghoneim MM, Johnson GM, Gormezano I (1994) Effects of subanesthetic concentrations of isoflurane and their interactions with epinephrine on acquisition and retention of the rabbit nictitating membrane response. Anesthesiology 81:229–237

    CAS  PubMed  Google Scholar 

  • Gormezano I, Schneiderman N, Deaux E, Fuentes I (1962) Nictitating membrane: classical conditioning and extinction in the albino rabbit. Science 138:33–34

    CAS  PubMed  Google Scholar 

  • Kehoe EJ, White NE (2002) Extinction revisited: similarities between extinction and reductions in US intensity in classical conditioning of the rabbit’s nictitating membrane response. Anim Learn Behav 30:96–111

    PubMed  Google Scholar 

  • Kehoe EJ, Ludvig EA, Sutton RS (2010) Timing in trace conditioning of the nictitating membrane response of the rabbit (Oryctolagus cuniculus): scalar, nonscalar, and adaptive features. Learn Mem 17:600–604

    PubMed  Google Scholar 

  • Longley M, Yeo CH (2014) Distribution of neural plasticity in cerebellum-dependent motor learning. Prog Brain Res 210:79–101

    PubMed  Google Scholar 

  • McCormick DA, Thompson RF (1984a) Cerebellum: essential involvement in the classically conditioned eyelid response. Science 223:296–299

    CAS  PubMed  Google Scholar 

  • McCormick DA, Thompson RF (1984b) Neuronal responses of the rabbit cerebellum during acquisition and performance of a classically conditioned nictitating membrane-eyelid response. J Neurosci 4:2811–2822

    CAS  PubMed  Google Scholar 

  • Napier RM, Macrae M, Kehoe EJ (1992) Rapid reacquisition in conditioning of the rabbit’s nictitating membrane response. J Exp Psychol Anim Behav Process 18:182–192

    CAS  PubMed  Google Scholar 

  • Schindler CW, White MF, Goldberg SR (1990) Effects of morphine, ethylketocyclazocine, N-allylnormetazocine and naloxone on locomotor activity in the rabbit. Psychopharmacology (Berl) 101:172–177

    CAS  Google Scholar 

  • Siegel JJ (2014) Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning. J Neurophysiol 112:2123–2137

    PubMed Central  PubMed  Google Scholar 

  • Solomon PR, Groccia-Ellison ME (1996) Classic conditioning in aged rabbits: delay, trace, and long-delay conditioning. Behav Neurosci 110:427–435

    CAS  PubMed  Google Scholar 

  • Solomon PR, Pendlebury WW (1988) A model systems approach to age-related memory disorders. Neurotoxicology 9:443–461

    CAS  PubMed  Google Scholar 

  • Woodruff-Pak DS, Li YT (1994) Nefiracetam (DM-9384): effect on eyeblink classical conditioning in older rabbits. Psychopharmacology (Berl) 114:200–208

    CAS  Google Scholar 

  • Woodruff-Pak DS, Li YT, Kem WR (1994) A nicotinic agonist (GTS-21), eyeblink classical conditioning, and nicotinic receptor binding in rabbit brain. Brain Res 645:309–317

    CAS  PubMed  Google Scholar 

  • Woodruff-Pak DS, Green JT, Pak JT, Shiotani T, Watabe S, Tanaka M (2002) The long-term effects of nefiracetam on learning in older rabbits. Behav Brain Res 136:299–308

    CAS  PubMed  Google Scholar 

  • Yokel RA, Provan SD, Meyer JJ, Campbell SR (1988) Aluminum intoxication and the victim of Alzheimer’s disease: similarities and differences. Neurotoxicology 9:429–442

    CAS  PubMed  Google Scholar 

  • Zbarska S, Bracha V (2012) Assessing the role of inferior olivary sensory signaling in the expression of conditioned eyeblinks using a combined glutamate/GABAA receptor antagonist protocol. J Neurophysiol 107:273–282

    PubMed Central  CAS  PubMed  Google Scholar 

Conditioned Taste Aversion

  • Cobuzzi JL, Siletti KA, Hurwitz ZE, Wetzell B, Baumann MH, Riley AL (2014) Age differences in (+/−) 3,4-methylenedioxymethamphetamine (MDMA)-induced conditioned taste aversions and monoaminergic levels. Dev Psychobiol 56:635–646

    PubMed Central  CAS  PubMed  Google Scholar 

  • Garcia J, Kimeldorf DJ, Koelling RA (1955) Conditioned aversion to saccharin resulting from exposure to gamma radiation. Science 122:157–158

    CAS  PubMed  Google Scholar 

  • Jones JD, Hall FS, Uhl GR, Rice K, Riley AL (2009) Differential involvement of the norepinephrine, serotonin and dopamine reuptake transporter proteins in cocaine-induced taste aversion. Pharmacol Biochem Behav 93:75–81

    PubMed Central  CAS  PubMed  Google Scholar 

  • Nachman M (1963) Learned aversion to the taste of lithium chloride and generalization to other salts. J Comp Physiol Psychol 56:343–349

    CAS  PubMed  Google Scholar 

  • Riley AL, Tuck DL (1985) Conditioned taste aversions: a behavioral index of toxicity. Ann N Y Acad Sci 443:272–292

    CAS  PubMed  Google Scholar 

  • Roma PG, Flint WW, Higley JD, Riley AL (2006) Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats. Psychopharmacology (Berl) 189:187–199

    CAS  Google Scholar 

  • Roma PG, Davis CM, Kohut SJ, Huntsberry ME, Riley AL (2008a) Early maternal separation and sex differences in the aversive effects of amphetamine in adult rats. Physiol Behav 93:897–904

    CAS  PubMed  Google Scholar 

  • Roma PG, Rinker JA, Serafine KM, Chen SA, Barr CS, Cheng K, Rice KC, Riley AL (2008b) Genetic and early environmental contributions to alcohol’s aversive and physiological effects. Pharmacol Biochem Behav 91:134–139

    PubMed Central  CAS  PubMed  Google Scholar 

  • Serafine KM, Briscione MA, Rice KC, Riley AL (2012) Dopamine mediates cocaine-induced conditioned taste aversions as demonstrated with cross-drug preexposure to GBR 12909. Pharmacol Biochem Behav 102:269–274

    CAS  PubMed  Google Scholar 

  • Verendeev A, Riley AL (2012) Conditioned taste aversion and drugs of abuse: history and interpretation. Neurosci Biobehav Rev 36:2193–2205

    PubMed  Google Scholar 

  • Wetzell BB, Muller MM, Cobuzzi JL, Hurwitz ZE, DeCicco-Skinner K, Riley AL (2014) Effect of age on methylphenidate-induced conditioned taste avoidance and related BDNF/TrkB signaling in the insular cortex of the rat. Psychopharmacology (Berl) 231:1493–1501

    CAS  Google Scholar 

Instrumental Conditioning

  • Mackintosh NJ (1974) The psychology of animal learning. Academic, London/New York

    Google Scholar 

  • Rescorla RA, Solomon RL (1967) Two-process learning theory: relationships between Pavlovian conditioning and instrumental learning. Psychol Rev 74:151–182

    CAS  PubMed  Google Scholar 

  • Skinner BF (1938) The behavior of organisms; an experimental analysis. D. Appleton-Century Company, New York/London

    Google Scholar 

  • Thorndike EL (1911) Animal intelligence experimental studies. Macmillan, New York

    Google Scholar 

Avoidance Learning

  • Colwill RC, Rescorla RA (1986) Associative structures in instrumental learning. In: Bower GH (ed) The psychology of learning and motivation, vol 20. Academic, New York, pp 55–104

    Google Scholar 

  • Crawford M, Masterson FA (1982) Species-specific defense reactions and avoidance learning. An evaluative review. Pavlov J Biol Sci 17(4):204–214

    CAS  PubMed  Google Scholar 

  • Di Scala G, Sandner G (1989) Conditioned place aversion produced by FG 7142 is attenuated by haloperidol. Psychopharmacology (Berl) 99(2):176–180

    Google Scholar 

  • Herrnstein RJ (1969) Method and theory in the study of avoidance. Psychol Rev 76(1):49–69

    CAS  PubMed  Google Scholar 

  • Tzschentke TM (2007) Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade. Addict Biol 12(3–4):227–462

    CAS  PubMed  Google Scholar 

Step-Down Inhibitory Avoidance

  • Aguggia JP, Suarez MM, Rivarola MA (2013) Early maternal separation: neurobehavioral consequences in mother rats. Behav Brain Res 248:25–31

    PubMed  Google Scholar 

  • Cheng L, Wang SH, Chen QC, Liao XM (2011) Moderate noise induced cognition impairment of mice and its underlying mechanisms. Physiol Behav 104:981–988

    CAS  PubMed  Google Scholar 

  • Fowler SW, Ramsey AK, Walker JM, Serfozo P, Olive MF, Schachtman TR, Simonyi A (2011) Functional interaction of mGlu5 and NMDA receptors in aversive learning in rats. Neurobiol Learn Mem 95:73–79

    PubMed Central  CAS  PubMed  Google Scholar 

  • Furini CR, Myskiw JC, Schmidt BE, Marcondes LA, Izquierdo I (2014) D1 and D5 dopamine receptors participate on the consolidation of two different memories. Behav Brain Res 271:212–217

    CAS  PubMed  Google Scholar 

  • Garcia-Gutierrez MS, Ortega-Alvaro A, Busquets-Garcia A, Perez-Ortiz JM, Caltana L, Ricatti MJ, Brusco A, Maldonado R, Manzanares J (2013) Synaptic plasticity alterations associated with memory impairment induced by deletion of CB2 cannabinoid receptors. Neuropharmacology 73:388–396

    CAS  PubMed  Google Scholar 

  • Goncalves JF, Nicoloso FT, da Costa P, Farias JG, Carvalho FB, da Rosa MM, Gutierres JM, Abdalla FH, Pereira JS, Dias GR, Barbosa NB, Dressler VL, Rubin MA, Morsch VM, Schetinger MR (2012) Behavior and brain enzymatic changes after long-term intoxication with cadmium salt or contaminated potatoes. Food Chem Toxicol 50:3709–3718

    CAS  PubMed  Google Scholar 

  • Harvey AL, Young LC, Kornisiuk E, Snitcofsky M, Colettis N, Blanco C, Jerusalinsky D, Jamieson AG, Hartley RC, Stone TW (2012) A novel dihydro-pyrazolo(3,4d)(1,2,4)triazolo(1,5a)pyrimidin-4-one (AJ23) is an antagonist at adenosine A(1) receptors and enhances consolidation of step-down avoidance. Behav Brain Res 234:184–191

    CAS  PubMed  Google Scholar 

  • Hudson BB (1939) One-trial learning in rats. Psychol Bull 36:643

    Google Scholar 

  • Jarvik ME, Essman WB (1960) A simple one-trial learning situation for mice. Psychol Rep 6:290

    Google Scholar 

  • Moojen VK, Damiani-Neves M, Bavaresco DV, Pescador BB, Comim CM, Quevedo J, Boeck CR (2012) NMDA preconditioning prevents object recognition memory impairment and increases brain viability in mice exposed to traumatic brain injury. Brain Res 1466:82–90

    CAS  PubMed  Google Scholar 

  • Myslivecek J, Hassmannova J (1991) Step-down passive avoidance in the rat ontogeny. Acta Neurobiol Exp 51:89–96

    CAS  Google Scholar 

  • Ortega-Alvaro A, Aracil-Fernandez A, Garcia-Gutierrez MS, Navarrete F, Manzanares J (2011) Deletion of CB2 cannabinoid receptor induces schizophrenia-related behaviors in mice. Neuropsychopharmacol 36:1489–1504

    CAS  Google Scholar 

  • Santos TB, Cespedes IC, Viana MB (2014) Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity. Behav Brain Res 267:46–54

    CAS  PubMed  Google Scholar 

  • Souza AC, Bruning CA, Acker CI, Neto JS, Nogueira CW (2013a) 2-Phenylethynyl-butyltellurium enhances learning and memory impaired by scopolamine in mice. Behav Pharmacol 24:249–254

    CAS  PubMed  Google Scholar 

  • Souza AC, Sari MH, Pinton S, Luchese C, Neto JS, Nogueira CW (2013b) 2-Phenylethynyl-butyltellurium attenuates amyloid-beta peptide(25–35)-induced learning and memory impairments in mice. J Neurosci Res 91:848–853

    CAS  PubMed  Google Scholar 

  • Vignisse J, Steinbusch HW, Bolkunov A, Nunes J, Santos AI, Grandfils C, Bachurin S, Strekalova T (2011) Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice. Prog Neuropsychopharmacol Biol Psychiatry 35:510–522

    CAS  PubMed  Google Scholar 

  • Zarrindast MR, Mashayekhi M, Rezayof A, Ahmadi S (2013) beta-Adrenoceptors in the dorsal hippocampus are involved in ethanol-induced state-dependent retrieval in mice. Neurobiol Learn Mem 100:12–17

    CAS  PubMed  Google Scholar 

Step-Through Inhibitory Avoidance

  • Akar F, Mutlu O, Komsuoglu Celikyurt I, Ulak G, Erden F, Bektas E, Tanyeri P (2014) Zaprinast and rolipram enhances spatial and emotional memory in the elevated plus maze and passive avoidance tests and diminishes exploratory activity in naive mice. Med Sci Monit Basic Res 20:105–111

    PubMed Central  PubMed  Google Scholar 

  • Banfi S, Cornelli U, Fonio W, Doricotti L (1982) A screening method for substances potentially active on learning and memory. J Pharmacol Methods 8:255–263

    CAS  PubMed  Google Scholar 

  • Broekkamp CL, O’Connor WT, Tonnaer JADM, Rijk HW, Van Delft AML (1986) Corticosterone, choline acetyltransferase and noradrenaline levels in olfactory bulbectomized rats in relation to changes in passive avoidance acquisition and open field activity. Physiol Behav 37:429–434

    CAS  PubMed  Google Scholar 

  • Bures J, Buresova W (1963) Cortical spreading depression as a memory disturbing factor. J Comp Physiol Psychol 56:268–272

    CAS  PubMed  Google Scholar 

  • Essman WB, Sudak TN (1964) Single-trial avoidance conditioning in rats. Psychol Rep 15:775–783

    Google Scholar 

  • Fekete M, De Wied D (1982) Potency and duration of action of the ACTH 4–9 analog (ORG 2766) as compared to ACTH 4–10 and [D-Phe7] ACTH 4–10 on active and passive avoidance behavior of rats. Pharmacol Biochem Behav 16:387–392

    CAS  PubMed  Google Scholar 

  • Fornari RV, Wichmann R, Atucha E, Desprez T, Eggens-Meijer E, Roozendaal B (2012) Involvement of the insular cortex in regulating glucocorticoid effects on memory consolidation of inhibitory avoidance training. Front Behav Neurosci 6:10

    PubMed Central  PubMed  Google Scholar 

  • Frye CA, Rhodes ME, Dudek B (2005) Estradiol to aged female or male mice improves learning in inhibitory avoidance and water maze tasks. Brain Res 1036:101–108

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hock FJ, Gerhards HJ, Wiemer G, Stechl J, Rüger W, Urbach H (1989) Effects of the novel compound, Hoe 065, upon impaired learning and memory in rodents. Eur J Pharmacol 171:79–85

    CAS  PubMed  Google Scholar 

  • Hudson BB (1950) One-trial learning in the domestic rat. Genet Psychol Monogr 41:99–147

    CAS  PubMed  Google Scholar 

  • Hughes CW (1976) Shock vs. ice-water passive avoidance learning in wild and domestic Rattus norvegicus. Learn Behav 4:66–70

    Google Scholar 

  • Kurtz KH, Pearl J (1960) The effects of prior fear experiences on acquired-drive learning. J Comp Physiol Psychol 53:201–206

    CAS  PubMed  Google Scholar 

  • Morris KA, Gold PE (2012) Age-related impairments in memory and in CREB and pCREB expression in hippocampus and amygdala following inhibitory avoidance training. Mech Ageing Dev 133:291–299

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sanchez-Resendis O, Medina AC, Serafín N, Prado-Alcalá RA, Roozendaal B, Quirarte GL (2012) Glucocorticoid-cholinergic interactions in the dorsal striatum in memory consolidation of inhibitory avoidance training. Front Behav Neurosci 6:1–8

    Google Scholar 

  • Zhang Y, Fukushima H, Kida S (2011) Induction and requirement of gene expression in the anterior cingulate cortex and medial prefrontal cortex for the consolidation of inhibitory avoidance memory. Mol Brain 4:1–11

    CAS  Google Scholar 

One-Way Avoidance

  • Boivin GA, Beninger RJ (2008) Differential effects of dopamine and AMPA receptor antagonists on the expression of conditioned avoidance responding in rats. Behav Neurosci 122:377–384

    CAS  PubMed  Google Scholar 

  • Duffy KB, Spangler EL, Devan BD, Guo Z, Bowker JL, Janas AM, Hagepanos A, Minor RK, DeCabo R, Mouton PR, Shukitt-Hale B, Joseph JA, Ingram DK (2008) A blueberry-enriched diet provides cellular protection against oxidative stress and reduces a kainate-induced learning impairment in rats. Neurobiol Aging 29:1680–1689

    CAS  PubMed  Google Scholar 

  • Gebhardt N, Bar KJ, Boettger MK, Grecksch G, Keilhoff G, Reichart R, Becker A (2013) Vagus nerve stimulation ameliorated deficits in one-way active avoidance learning and stimulated hippocampal neurogenesis in bulbectomized rats. Brain Stimul 6:78–83

    PubMed  Google Scholar 

  • Hock FJ, McGaugh JL (1985) Enhancing effects of Hoe 175 on memory in mice. Psychopharmacology (Berl) 86:114–117

    CAS  Google Scholar 

  • Lubar JF, Perachio AA (1965) One-way and two-way learning and transfer of an active avoidance response in normal and cingulectomized cats. J Comp Physiol Psychol 60:46–52

    CAS  PubMed  Google Scholar 

  • Martinez JL Jr, Hernandez RV, Rodriguez SB (1992) D-Pen2-[D-Pen5]enkephalin impairs acquisition and enhances retention of a one-way active avoidance response in rats. Peptides 13:885–889

    CAS  PubMed  Google Scholar 

  • Maul B, von Bohlen und Halbach O, Becker A, Sterner-Kock A, Voigt JP, Siems WE, Grecksch G, Walther T (2008) Impaired spatial memory and altered dendritic spine morphology in angiotensin II type 2 receptor-deficient mice. J Mol Med 86:563–571

    CAS  PubMed  Google Scholar 

  • McKean DB, Pearl J (1968) Avoidance box for mice. Physiol Behav 3:795–796

    Google Scholar 

  • Munn NL (1950) Handbook of psychological research on the rat; an introduction to animal psychology. Houghton Mifflin, Boston

    Google Scholar 

  • Tenen SS (1966) An automated one-way avoidance box for the rat. Psychon Sci 6:407–408

    Google Scholar 

Two-Way Avoidance

  • Choi JS, Cain CK, LeDoux JE (2010) The role of amygdala nuclei in the expression of auditory signaled two-way active avoidance in rats. Learn Mem 17:139–147

    PubMed Central  PubMed  Google Scholar 

  • Datta S, Siwek DF, Huang MP (2009) Improvement of two-way active avoidance memory requires protein kinase a activation and brain-derived neurotrophic factor expression in the dorsal hippocampus. J Mol Neurosci MN 38:257–264

    CAS  PubMed  Google Scholar 

  • Ilango A, Shumake J, Wetzel W, Scheich H, Ohl FW (2011) Effects of ventral tegmental area stimulation on the acquisition and long-term retention of active avoidance learning. Behav Brain Res 225:515–521

    PubMed  Google Scholar 

  • Lichtenberg NT, Kashtelyan V, Burton AC, Bissonette GB, Roesch MR (2014) Nucleus accumbens core lesions enhance two-way active avoidance. Neuroscience 258:340–346

    PubMed Central  CAS  PubMed  Google Scholar 

  • Wietzikoski EC, Boschen SL, Miyoshi E, Bortolanza M, Dos Santos LM, Frank M, Brandao ML, Winn P, Da Cunha C (2012) Roles of D1-like dopamine receptors in the nucleus accumbens and dorsolateral striatum in conditioned avoidance responses. Psychopharmacology (Berl) 219:159–169

    CAS  Google Scholar 

Operant Learning

  • Aggleton JP, Keen S, Warburton EC, Bussey TJ (1997) Extensive cytotoxic lesions involving both the rhinal cortices and area TE impair recognition but spare spatial alternation in the rat. Brain Res Bull 43:279–287

    CAS  PubMed  Google Scholar 

  • Crawley JN (2007) What’s wrong with my mouse?: behavioral phenotyping of transgenic and knockout mice, 2nd edn. Wiley-Interscience, Hoboken

    Google Scholar 

  • Mackintosh NJ (1974) The psychology of animal learning. Academic, London/New York

    Google Scholar 

  • Romberg C, Horner AE, Bussey TJ, Saksida LM (2013) A touch screen-automated cognitive test battery reveals impaired attention, memory abnormalities, and increased response inhibition in the TgCRND8 mouse model of Alzheimer’s disease. Neurobiol Aging 34:731–744

    PubMed Central  PubMed  Google Scholar 

Discrimination Learning

  • Bussey TJ, Holmes A, Lyon L, Mar AC, McAllister KA, Nithianantharajah J, Oomen CA, Saksida LM (2012) New translational assays for preclinical modelling of cognition in schizophrenia: the touchscreen testing method for mice and rats. Neuropharmacology 62:1191–1203

    PubMed Central  CAS  PubMed  Google Scholar 

  • Gilbert RM, Sutherland NS (1969) Animal discrimination learning. Academic, London/New York

    Google Scholar 

  • Mackintosh NJ (1974) The psychology of animal learning. Academic, London/New York

    Google Scholar 

Spatial Discrimination

  • Barnes CA (1979) Memory deficits associated with senescence: A neurophysiological and behavioral study in the rat. J Comp Physiol Psychol 93:74–104

    CAS  PubMed  Google Scholar 

  • Deacon RM (2006) Appetitive position discrimination in the T-maze. Nat Protoc 1:13–15

    PubMed  Google Scholar 

  • Derenne A, Brown-Borg HM, Martner S, Wolff W, Frerking M (2014) Spatial delayed nonmatching-to-sample performances in long-living Ames dwarf mice. Physiol Behav 123:100–104

    CAS  PubMed  Google Scholar 

  • Fidalgo C, Conejo NM, Gonzalez-Pardo H, Arias JL (2012) Functional interaction between the dorsal hippocampus and the striatum in visual discrimination learning. J Neurosci Res 90:715–720

    CAS  PubMed  Google Scholar 

  • Fowler SW, Walker JM, Klakotskaia D, Will MJ, Serfozo P, Simonyi A, Schachtman TR (2013) Effects of a metabotropic glutamate receptor 5 positive allosteric modulator, CDPPB, on spatial learning task performance in rodents. Neurobiol Learn Mem 99:25–31

    CAS  PubMed  Google Scholar 

  • Gaskill BN, Lucas JR, Pajor EA, Garner JP (2011) Little and often? Maintaining continued performance in an automated T-maze for mice. Behav Processes 86:272–278

    PubMed  Google Scholar 

  • Hallock HL, Arreola AC, Shaw CL, Griffin AL (2013) Dissociable roles of the dorsal striatum and dorsal hippocampus in conditional discrimination and spatial alternation T-maze tasks. Neurobiol Learn Mem 100:108–116

    PubMed  Google Scholar 

  • Hammond R, Nelson D, Kline E, Gibbs RB (2012) Chronic treatment with a GPR30 antagonist impairs acquisition of a spatial learning task in young female rats. Horm Behav 62:367–374

    PubMed Central  CAS  PubMed  Google Scholar 

  • Murray CL, Obiang P, Bannerman D, Cunningham C (2013) Endogenous IL-1 in cognitive function and anxiety: a study in IL-1RI−/− mice. PLoS One 8:e78385

    PubMed Central  CAS  PubMed  Google Scholar 

  • Sanderson DJ, Rawlins JN, Deacon RM, Cunningham C, Barkus C, Bannerman DM (2012) Hippocampal lesions can enhance discrimination learning despite normal sensitivity to interference from incidental information. Hippocampus 22:1553–1566

    PubMed Central  PubMed  Google Scholar 

  • Sharma S, Rakoczy S, Brown-Borg H (2010) Assessment of spatial memory in mice. Life Sci 87:521–536

    CAS  PubMed  Google Scholar 

  • Thorpe CM, Jacova C, Wilkie DM (2004) Some pitfalls in measuring memory in animals. Neurosci Biobehav Rev 28:711–718

    PubMed  Google Scholar 

Visual Discrimination

  • Bari A, Robbins TW (2013) Inhibition and impulsivity: behavioral and neural basis of response control. Prog Neurobiol 108:44–79

    PubMed  Google Scholar 

  • Bari A, Dalley JW, Robbins TW (2008) The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats. Nat Protoc 3:759–767

    CAS  PubMed  Google Scholar 

  • Bevins RA, Besheer J (2006) Object recognition in rats and mice: a one-trial non-matching-to-sample learning task to study ‘recognition memory’. Nat Protoc 1:1306–1311

    PubMed  Google Scholar 

  • Bussey TJ, Muir JL, Everitt BJ, Robbins TW (1997) Triple dissociation of anterior cingulate, posterior cingulate, and medial frontal cortices on visual discrimination tasks using a touchscreen testing procedure for the rat. Behav Neurosci 111:920–936

    CAS  PubMed  Google Scholar 

  • Bussey TJ, Holmes A, Lyon L, Mar AC, McAllister KA, Nithianantharajah J, Oomen CA, Saksida LM (2012) New translational assays for preclinical modelling of cognition in schizophrenia: the touchscreen testing method for mice and rats. Neuropharmacology 62:1191–1203

    PubMed Central  CAS  PubMed  Google Scholar 

  • Carli M, Robbins TW, Evenden JL, Everitt BJ (1983) Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9:361–380

    CAS  PubMed  Google Scholar 

  • Harrison AA, Everitt BJ, Robbins TW (1997) Central 5-HT depletion enhances impulsive responding without affecting the accuracy of attentional performance: interactions with dopaminergic mechanisms. Psychopharmacology (Berl) 133:329–342

    CAS  Google Scholar 

  • Horner AE, Heath CJ, Hvoslef-Eide M, Kent BA, Kim CH, Nilsson SR, Alsio J, Oomen CA, Holmes A, Saksida LM, Bussey TJ (2013) The touchscreen operant platform for testing learning and memory in rats and mice. Nat Protoc 8:1961–1984

    PubMed Central  CAS  PubMed  Google Scholar 

  • Lustig C, Kozak R, Sarter M, Young JW, Robbins TW (2013) CNTRICS final animal model task selection: control of attention. Neurosci Biobehav Rev 37:2099–2110

    CAS  PubMed  Google Scholar 

  • Marston HM, Everitt BJ, Robbins TW (1993) Comparative effects of excitotoxic lesions of the hippocampus and septum/diagonal band on conditional visual discrimination and spatial learning. Neuropsychologia 31:1099–1118

    CAS  PubMed  Google Scholar 

  • Muir JL, Robbins TW, Everitt BJ (1992) Disruptive effects of muscimol infused into the basal forebrain on conditional discrimination and visual attention: differential interactions with cholinergic mechanisms. Psychopharmacology (Berl) 107:541–550

    CAS  Google Scholar 

  • Reading PJ, Dunnett SB, Robbins TW (1991) Dissociable roles of the ventral, medial and lateral striatum on the acquisition and performance of a complex visual stimulus–response habit. Behav Brain Res 45:147–161

    CAS  PubMed  Google Scholar 

  • Romberg C, Horner AE, Bussey TJ, Saksida LM (2013) A touch screen-automated cognitive test battery reveals impaired attention, memory abnormalities, and increased response inhibition in the TgCRND8 mouse model of Alzheimer’s disease. Neurobiol Aging 34:731–744

    PubMed Central  PubMed  Google Scholar 

  • Steckler T, Drinkenburg WH, Sahgal A, Aggleton JP (1998) Recognition memory in rats–I. Concepts and classification. Prog Neurobiol 54:289–311

    CAS  PubMed  Google Scholar 

  • Winters BD, Robbins TW, Everitt BJ (2004) Selective cholinergic denervation of the cingulate cortex impairs the acquisition and performance of a conditional visual discrimination in rats. Eur J Neurosci 19:490–496

    PubMed  Google Scholar 

Spatial Learning

  • Paul CM, Magda G, Abel S (2009) Spatial memory: theoretical basis and comparative review on experimental methods in rodents. Behav Brain Res 203(2):151–164

    PubMed  Google Scholar 

  • Sharma S, Rakoczy S, Brown-Borg H (2010) Assessment of spatial memory in mice. Life Sci 87(17–18):521–536

    CAS  PubMed  Google Scholar 

  • Silva AJ, Giese KP, Fedorov NB, Frankland PW, Kogan JH (1998) Molecular, cellular, and neuroanatomical substrates of place learning. Neurobiol Learn Mem 70(1–2):44–61

    CAS  PubMed  Google Scholar 

  • Stone CP (1929) The age factor in animal learning. Clark University, Worcester

    Google Scholar 

Spatial Habituation Learning

  • Berlyne DE (1960) Conflict, arousal, and curiosity. McGraw-Hill, New York

    Google Scholar 

  • Brenes JC, Padilla M, Fornaguera J (2009) A detailed analysis of open-field habituation and behavioral and neurochemical antidepressant-like effects in postweaning enriched rats. Behav Brain Res 197:125–137

    CAS  PubMed  Google Scholar 

  • de Oliveira Alvares L, de Oliveira LF, Camboim C, Diehl F, Genro BP, Lanziotti VB, Quillfeldt JA (2005) Amnestic effect of intrahippocampal AM251, a CB1-selective blocker, in the inhibitory avoidance, but not in the open field habituation task, in rats. Neurobiol Learn Mem 83:119–124

    PubMed  Google Scholar 

  • Deacon RM, Koros E, Bornemann KD, Rawlins JN (2009) Aged Tg2576 mice are impaired on social memory and open field habituation tests. Behav Brain Res 197:466–468

    CAS  PubMed  Google Scholar 

  • Geyer MA, Russo PV, Masten VL (1986) Multivariate assessment of locomotor behavior: pharmacological and behavioral analyses. Pharmacol Biochem Behav 25:277–288

    CAS  PubMed  Google Scholar 

  • Guzowski JF, Miyashita T, Chawla MK, Sanderson J, Maes LI, Houston FP, Lipa P, McNaughton BL, Worley PF, Barnes CA (2006) Recent behavioral history modifies coupling between cell activity and Arc gene transcription in hippocampal CA1 neurons. Proc Natl Acad Sci U S A 103:1077–1082

    PubMed Central  CAS  PubMed  Google Scholar 

  • Hall FS, Huang S, Fong GW, Sundstrom JM, Pert A (2000) Differential basis of strain and rearing effects on open-field behavior in Fawn Hooded and Wistar rats. Physiol Behav 71:525–532

    CAS  PubMed  Google Scholar 

  • Hinde RA (1970) Animal behaviour; a synthesis of ethology and comparative psychology, 2nd edn. McGraw-Hill, New York

    Google Scholar 

  • Lee M, Chen K, Shih JC, Hiroi N (2004) MAO-B knockout mice exhibit deficient habituation of locomotor activity but normal nicotine intake. Genes Brain Behav 3:216–227

    CAS  PubMed  Google Scholar 

  • Milot M, Plamondon H (2008) Ischemia-induced hyperactivity: effects of dim versus bright illumination on open-field exploration and habituation following global ischemia in rats. Behav Brain Res 192:166–172

    PubMed  Google Scholar 

  • Pinsker H, Kandel ER, Castellucci V, Kupfermann I (1970a) An analysis of habituation and dishabituation in Aplysia. Adv Biochem Psychopharmacol 2:351–373

    CAS  PubMed  Google Scholar 

  • Pinsker H, Kupfermann I, Castellucci V, Kandel E (1970b) Habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science 167:1740–1742

    CAS  PubMed  Google Scholar 

  • Popovic N, Caballero-Bleda M, Popovic M (2014) Post-training scopolamine treatment induced maladaptive behavior in open field habituation task in rats. PloS One 9:e100348

    PubMed Central  PubMed  Google Scholar 

  • Thompson RF, Spencer WA (1966) Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev 73:16–43

    CAS  PubMed  Google Scholar 

Radial Arm Maze

  • Buresova O, Bures J, Oitzl MS, Zahalka A (1985) Radial maze in the water tank: an aversively motivated spatial working memory task. Physiol Behav 34:1003–1005

    CAS  PubMed  Google Scholar 

  • Dubreuil D, Tixier C, Dutrieux G, Edeline JM (2003) Does the radial arm maze necessarily test spatial memory? Neurobiol Learn Mem 79:109–117

    PubMed  Google Scholar 

  • Floresco SB, Seamans JK, Phillips AG (1997) Selective roles for hippocampal, prefrontal cortical, and ventral striatal circuits in radial-arm maze tasks with or without a delay. J Neurosci 17:1880–1890

    CAS  PubMed  Google Scholar 

  • McDonald RJ, White NM (2013) A triple dissociation of memory systems: hippocampus, amygdala, and dorsal striatum. Behav Neurosci 127:835–853

    PubMed  Google Scholar 

  • Olton DS, Samuelson RJ (1976) Remembrance of places passed: spatial memory in rats. J Exp Psychol Anim Behav Process 2:97–116

    Google Scholar 

  • Penley SC, Gaudet CM, Threlkeld SW (2013) Use of an eight-arm radial water maze to assess working and reference memory following neonatal brain injury. J Vis Exp 50940

    Google Scholar 

  • Petkova Z, Tchekalarova J, Pechlivanova D, Moyanova S, Kortenska L, Mitreva R, Popov D, Markova P, Lozanov V, Atanasova D, Lazarov N, Stoynev A (2014) Treatment with melatonin after status epilepticus attenuates seizure activity and neuronal damage but does not prevent the disturbance in diurnal rhythms and behavioral alterations in spontaneously hypertensive rats in kainate model of temporal lobe epilepsy. Epilepsy Behav 31:198–208

    PubMed  Google Scholar 

  • Vorhees CV, Williams MT (2014) Assessing spatial learning and memory in rodents. ILAR J 55:310–332

    PubMed Central  CAS  PubMed  Google Scholar 

The Morris Water Maze

  • Able JA, Gudelsky GA, Vorhees CV, Williams MT (2006) 3,4-Methylenedioxymethamphetamine in adult rats produces deficits in path integration and spatial reference memory. Biol Psychiatry 59:1219–1226

    PubMed Central  CAS  PubMed  Google Scholar 

  • Darcet F, Mendez-David I, Tritschler L, Gardier AM, Guilloux J-P, David DJ (2014) Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression. Front Behav Neurosci 8:136

    PubMed Central  PubMed  Google Scholar 

  • Fan G, Feng C, Wu F, Ye W, Lin F, Wang C, Yan J, Zhu G, Xiao Y, Bi Y (2010) Methionine choline reverses lead-induced cognitive and N-methyl-d-aspartate receptor subunit 1 deficits. Toxicology 272:23–31

    CAS  PubMed  Google Scholar 

  • Jiang S, Su J, Yao S, Zhang Y, Cao F, Wang F, Wang H, Li J, Xi S (2014) Fluoride and arsenic exposure impairs learning and memory and decreases mGluR5 expression in the hippocampus and cortex in rats. PLoS One 9:e96041

    PubMed Central  PubMed  Google Scholar 

  • McAuliffe JJ, Miles L, Vorhees CV (2006) Adult neurological function following neonatal hypoxia-ischemia in a mouse model of the term neonate: water maze performance is dependent on separable cognitive and motor components. Brain Res 1118:208–221

    CAS  PubMed  Google Scholar 

  • Morris RGM (1981) Spatial localization does not require the presence of local cues. Learn Motiv 12:239–260

    Google Scholar 

  • Morris R (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 11:47–60

    CAS  PubMed  Google Scholar 

  • Schaefer TL, Lingrel JB, Moseley AE, Vorhees CV, Williams MT (2011) Targeted mutations in the Na, K-ATPase alpha 2 isoform confer ouabain resistance and result in abnormal behavior in mice. Synapse 65:520–531

    PubMed Central  CAS  PubMed  Google Scholar 

  • Skelton MR, Williams MT, Vorhees CV (2006) Treatment with MDMA from P11-20 disrupts spatial learning and path integration learning in adolescent rats but only spatial learning in older rats. Psychopharmacology (Berl) 189:307–318

    CAS  Google Scholar 

  • Vorhees CV, Williams MT (2006) Morris water maze: procedures for assessing spatial and related forms of learning and memory. Nat Protoc 1:848–858

    PubMed Central  PubMed  Google Scholar 

  • Vorhees CV, Williams MT (2014) Assessing spatial learning and memory in rodents. ILAR J 55:310–332

    PubMed Central  CAS  PubMed  Google Scholar 

Non-rodent Species Used in Learning and Memory Studies

  • Bachevalier J, Alvarado MC, Malkova L (1999) Memory and socioemotional behavior in monkeys after hippocampal damage incurred in infancy or in adulthood. Biol Psychiatry 46:329–339

    CAS  PubMed  Google Scholar 

  • Barbas H (2000) Connections underlying the synthesis of cognition, memory, and emotion in primate prefrontal cortices. Brain Res Bull 52:319–330

    CAS  PubMed  Google Scholar 

  • Consortium CS (1998) Genome sequence of the nematode C. elegans: a platform for investigating biology. Science 282:2012–2018

    Google Scholar 

  • Fragaszy DM, Cummins-Sebree SE (2005) Relational spatial reasoning by a nonhuman: the example of capuchin monkeys. Behav Cogn Neurosci Rev 4:282–306

    PubMed  Google Scholar 

  • Hara Y, Rapp PR, Morrison JH (2012) Neuronal and morphological bases of cognitive decline in aged rhesus monkeys. Age (Dordr) 34:1051–1073

    Google Scholar 

  • Levin ED, Cerutti DT (2009) Behavioral neuroscience of zebrafish. In: Buccafusco JJ (ed) Methods of behavior analysis in neuroscience, Frontiers in neuroscience. CRC Press, Boca Raton

    Google Scholar 

  • Levy R, Goldman-Rakic PS (2000) Segregation of working memory functions within the dorsolateral prefrontal cortex. Exp Brain Res 133:23–32

    CAS  PubMed  Google Scholar 

  • Macpherson K, Roberts WA (2010) Spatial memory in dogs (Canis familiaris) on a radial maze. J Comp Psychol 124:47–56

    PubMed  Google Scholar 

  • Philippens IH, Melchers BP, Wolthuis OL (1992) Active avoidance behavior in guinea pigs: effects of physostigmine and scopolamine. Pharmacol Biochem Behav 42:285–289

    CAS  PubMed  Google Scholar 

  • Pinsker H, Kandel ER, Castellucci V, Kupfermann I (1970a) An analysis of habituation and dishabituation in Aplysia. Adv Biochem Psychopharmacol 2:351–373

    CAS  PubMed  Google Scholar 

  • Pinsker H, Kupfermann I, Castellucci V, Kandel E (1970b) Habituation and dishabituation of the gill-withdrawal reflex in Aplysia. Science 167:1740–1742

    CAS  PubMed  Google Scholar 

  • Rabe A, Haddad R, Dumas R (1985) Behavior and neurobehavioral teratology using the ferret. Lab Anim Sci 35:256–267

    CAS  PubMed  Google Scholar 

  • Roberts AC (1996) Comparison of cognitive function in human and non-human primates. Brain Res Cogn Brain Res 3:319–327

    CAS  PubMed  Google Scholar 

  • Roberts AC, Robbins TW, Everitt BJ (1988) The effects of intradimensional and extradimensional shifts on visual discrimination learning in humans and non-human primates. Q J Exp Psychol B Comp Physiol Psychol 40:321–341

    CAS  Google Scholar 

  • Sasakura H, Mori I (2013) Behavioral plasticity, learning, and memory in C. elegans. Curr Opin Neurobiol 23:92–99

    CAS  PubMed  Google Scholar 

  • Sondergaard LV, Ladewig J, Dagnaes-Hansen F, Herskin MS, Holm IE (2012) Object recognition as a measure of memory in 1–2 years old transgenic minipigs carrying the APPsw mutation for Alzheimer’s disease. Transgenic Res 21:1341–1348

    CAS  PubMed  Google Scholar 

  • Voytko ML (1996) Cognitive functions of the basal forebrain cholinergic system in monkeys: memory or attention? Behav Brain Res 75:13–25

    CAS  PubMed  Google Scholar 

  • Walker LC, Kitt CA, Struble RG, Wagster MV, Price DL, Cork LC (1988) The neural basis of memory decline in aged monkeys. Neurobiol Aging 9:657–666

    CAS  PubMed  Google Scholar 

  • Weller RE, LeDoux MS, Toll LM, Gould MK, Hicks RA, Cox JE (2006) Subdivisions of inferior temporal cortex in squirrel monkeys make dissociable contributions to visual learning and memory. Behav Neurosci 120:423–446

    PubMed  Google Scholar 

  • Wright NJ (2014) Evolution of the techniques used in studying associative olfactory learning and memory in adult Drosophila in vivo: a historical and technical perspective. Invert Neurosci 14:1–11

    CAS  PubMed  Google Scholar 

Models of Learning and Memory Impairments

  • Antuono P, Amaducci L, Pazzagli A, Pepeu G (1979) Psychopharmacological prospectives in the treatment of dementia. Prog Neuropsychopharmacol 3:75–80

    CAS  PubMed  Google Scholar 

  • Archer T, Kostrzewa RM, Beninger RJ, Palomo T (2011) Staging neurodegenerative disorders: structural, regional, biomarker, and functional progressions. Neurotox Res 19:211–234

    PubMed  Google Scholar 

  • Barnes P, Hale G, Good M (2004) Intramaze and extramaze cue processing in adult APPSWE Tg2576 transgenic mice. Behav Neurosci 118:1184–1195

    PubMed  Google Scholar 

  • Berry-Kravis E (2014) Mechanism-based treatments in neurodevelopmental disorders: fragile X syndrome. Pediatr Neurol 50:297–302

    PubMed  Google Scholar 

  • Butterfield DA (2002) Amyloid beta-peptide (1–42)-induced oxidative stress and neurotoxicity: implications for neurodegeneration in Alzheimer’s disease brain. A review. Free Radic Res 36:1307–1313

    CAS  PubMed  Google Scholar 

  • Carli M, Balducci C, Millan MJ, Bonalumi P, Samanin R (1999) S 15535, a benzodioxopiperazine acting as presynaptic agonist and postsynaptic 5-HT(1A) receptor antagonist, prevents the impairment of spatial learning caused by intrahippocampal scopolamine. Br J Pharmacol 128:1207–1214

    PubMed Central  CAS  PubMed  Google Scholar 

  • Castillo-Carranza DL, Guerrero-Munoz MJ, Sengupta U, Hernandez C, Barrett AD, Dineley K, Kayed R (2015) Tau immunotherapy modulates both pathological tau and upstream amyloid pathology in an Alzheimer’s disease mouse model. J Neurosci 35:4857–4868

    CAS  PubMed  Google Scholar 

  • Deacon RM, Koros E, Bornemann KD, Rawlins JN (2009) Aged Tg2576 mice are impaired on social memory and open field habituation tests. Behav Brain Res 197:466–468

    CAS  PubMed  Google Scholar 

  • Entlerova M, Lobellova V, Hatalova H, Zemanova A, Vales K, Stuchlik A (2013) Comparison of Long-Evans and Wistar rats in sensitivity to central cholinergic blockade with scopolamine in two spatial tasks: an active place avoidance and the Morris water maze. Physiol Behav 120:11–18

    CAS  PubMed  Google Scholar 

  • Everitt BJ, Robbins TW (1997) Central cholinergic systems and cognition. Annu Rev Psychol 48:649–684

    CAS  PubMed  Google Scholar 

  • Fox SH, Brotchie JM (2010) The MPTP-lesioned non-human primate models of Parkinson’s disease. Past, present, and future. Prog Brain Res 184:133–157

    CAS  PubMed  Google Scholar 

  • Fujimoto ST, Longhi L, Saatman KE, Conte V, Stocchetti N, McIntosh TK (2004) Motor and cognitive function evaluation following experimental traumatic brain injury. Neurosci Biobehav Rev 28:365–378

    PubMed  Google Scholar 

  • Gordan ML, Jungwirth B, Ohl F, Kellermann K, Kochs EF, Blobner M (2012) Evaluation of neurobehavioral deficits following different severities of cerebral ischemia in rats: a comparison between the modified hole board test and the Morris water maze test. Behav Brain Res 235:7–20

    PubMed  Google Scholar 

  • Henry JD, Phillips LH, Crawford JR, Kliegel M, Theodorou G, Summers F (2007) Traumatic brain injury and prospective memory: influence of task complexity. J Clin Exp Neuropsychol 29:457–466

    PubMed  Google Scholar 

  • Heo Y-M, Shin M-S, Kim S-H, Kim T-W, Baek S-B, Baek S-S (2014) Treadmill exercise ameliorates disturbance of spatial learning ability in scopolamine-induced amnesia rats. J Exerc Rehabil 10:155–161

    PubMed Central  PubMed  Google Scholar 

  • Hunter AJ, Mackay KB, Rogers DC (1998) To what extent have functional studies of ischaemia in animals been useful in the assessment of potential neuroprotective agents? Trends Pharmacol Sci 19:59–66

    CAS  PubMed  Google Scholar 

  • Klinkenberg I, Blokland A (2011) A comparison of scopolamine and biperiden as a rodent model for cholinergic cognitive impairment. Psychopharmacology (Berl) 215:549–566

    CAS  Google Scholar 

  • McAuliffe JJ, Miles L, Vorhees CV (2006) Adult neurological function following neonatal hypoxia-ischemia in a mouse model of the term neonate: water maze performance is dependent on separable cognitive and motor components. Brain Res 1118:208–221

    CAS  PubMed  Google Scholar 

  • Miyamoto M, Shintani M, Nagaoka A, Nagawa Y (1985) Lesioning of the rat basal forebrain leads to memory impairments in passive and active avoidance tasks. Brain Res 328:97–104

    CAS  PubMed  Google Scholar 

  • Moojen VK, Damiani-Neves M, Bavaresco DV, Pescador BB, Comim CM, Quevedo J, Boeck CR (2012) NMDA preconditioning prevents object recognition memory impairment and increases brain viability in mice exposed to traumatic brain injury. Brain Res 1466:82–90

    CAS  PubMed  Google Scholar 

  • Pepeu G, Casamenti F, Pedata F, Cosi C, Pepeu IM (1986) Are the neurochemical and behavioral changes induced by lesions of the nucleus basalis in the rat a model of Alzheimer’s disease? Prog Neuropsychopharmacol Biol Psychiatry 10:541–551

    CAS  PubMed  Google Scholar 

  • Philippens IH, Melchers BP, Wolthuis OL (1992) Active avoidance behavior in guinea pigs: effects of physostigmine and scopolamine. Pharmacol Biochem Behav 42:285–289

    CAS  PubMed  Google Scholar 

  • Popovic N, Caballero-Bleda M, Popovic M (2014) Post-training scopolamine treatment induced maladaptive behavior in open field habituation task in rats. PLoS One 9:e100348

    PubMed Central  PubMed  Google Scholar 

  • Robbins TW, McAlonan G, Muir JL, Everitt BJ (1997) Cognitive enhancers in theory and practice: studies of the cholinergic hypothesis of cognitive deficits in Alzheimer’s disease. Behav Brain Res 83:15–23

    CAS  PubMed  Google Scholar 

  • Roeltgen DP, Schneider JS (1994) Task persistence and learning ability in normal and chronic low dose MPTP-treated monkeys. Behav Brain Res 60:115–124

    CAS  PubMed  Google Scholar 

  • Scavio MJ, Clift PS, Wills JC (1992) Posttraining effects of amphetamine, chlorpromazine, ketamine, and scopolamine on the acquisition and extinction of the rabbit’s conditioned nictitating membrane response. Behav Neurosci 106:900–908

    CAS  PubMed  Google Scholar 

  • Schneider JS, Sun ZQ, Roeltgen DP (1994) Effects of dopamine agonists on delayed response performance in chronic low-dose MPTP-treated monkeys. Pharmacol Biochem Behav 48:235–240

    CAS  PubMed  Google Scholar 

  • Sethi P, Jyoti A, Singh R, Hussain E, Sharma D (2008) Aluminium-induced electrophysiological, biochemical and cognitive modifications in the hippocampus of aging rats. Neurotoxicology 29:1069–1079

    CAS  PubMed  Google Scholar 

  • Singer P, Yee BK (2012) Reversal of scopolamine-induced disruption of prepulse inhibition by clozapine in mice. Pharmacol Biochem Behav 101:107–114

    PubMed Central  CAS  PubMed  Google Scholar 

  • Solomon PR, Pendlebury WW (1988) A model systems approach to age-related memory disorders. Neurotoxicology 9:443–461

    CAS  PubMed  Google Scholar 

  • Souza AC, Sari MH, Pinton S, Luchese C, Neto JS, Nogueira CW (2013) 2-Phenylethynyl-butyltellurium attenuates amyloid-beta peptide(25–35)-induced learning and memory impairments in mice. J Neurosci Res 91:848–853

    CAS  PubMed  Google Scholar 

  • Webster SJ, Bachstetter AD, Nelson PT, Schmitt FA, Van Eldik LJ (2014) Using mice to model Alzheimer’s dementia: an overview of the clinical disease and the preclinical behavioral changes in 10 mouse models. Front Genet 5:88

    PubMed Central  PubMed  Google Scholar 

  • Wilson DA (2001) Scopolamine enhances generalization between odor representations in rat olfactory cortex. Learn Mem 8:279–285

    PubMed Central  CAS  PubMed  Google Scholar 

  • Woodruff-Pak DS, Hinchliffe RM (1997) Mecamylamine- or scopolamine-induced learning impairment: ameliorated by nefiracetam. Psychopharmacology (Berl) 131:130–139

    CAS  Google Scholar 

  • Yokel RA, Provan SD, Meyer JJ, Campbell SR (1988) Aluminum intoxication and the victim of Alzheimer’s disease: similarities and differences. Neurotoxicology 9:429–442

    CAS  PubMed  Google Scholar 

  • Young RS, Kolonich J, Woods CL, Yagel SK (1986) Behavioral performance of rats following neonatal hypoxia-ischemia. Stroke J Cereb Circ 17:1313–1316

    CAS  Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy and Pharmaceutical Sciences, Frederic and Mary Wolfe Center, Pharmacology Department, MS-1015, The University of Toledo, HSC, 3000 Arlington Avenue, Toledo, OH, 43614, USA

    F. Scott Hall & Yasir Saber

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  1. F. Scott Hall
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  2. Yasir Saber
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Correspondence to F. Scott Hall .

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  1. CorDynamics, Dieburg, Germany

    Franz J. Hock

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Hall, F.S., Saber, Y. (2016). Behavioral Methods Used in the Study of Learning and Memory. In: Hock, F. (eds) Drug Discovery and Evaluation: Pharmacological Assays. Springer, Cham. https://doi.org/10.1007/978-3-319-05392-9_37

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