Abstract
The elevated plus-maze consists of two open, elevated arms running along a north-south axis and two arms enclosed by walls running east-west. It combines elements of unfamiliarity, openness and elevation (see Chap. 16). Since its introduction by Handley and Mithani (1984) and experimental validation for rats (Pellow et al. 1985) and mice (Lister 1987), it has been most extensively used to asses anxiolytic and anxiogenic effects of drugs in several hundred studies. Standard anxiolytic and anxiogenic drugs increase and decrease, respectively, both the percentage of time that rats (or mice) spend in the open arms and the percentage of entries that they make into the open arms. However, due to its widespread appeal, the elevated plus-maze has also been used to measure levels of spontaneous anxiety behavior (Goto et al. 1993), to investigate anxiety-induced antinociception (Lee and Rodgers 1990; Frussa-Filho et al. 1992; Conceição et al. 1992; Rodgers et al. 1992) and to evaluate memory. Regarding this latter use, Itoh et al. (1990) proposed that the retesting-induced decrease in the time taken by the animal to move from an open arm to an enclosed arm in the elevated plus-maze could be a measure of memory. This suggestion has been corroborated and extended by others (Frussa-Filho et al. 1991; Graeff et al. 1993; Conceição et al. 1994). For example, Graeff et al. (1993) showed that the retesting-induced increase in the time taken by the animal to move from an enclosed arm to an open arm could be used as an inhibitory avoidance task to measure memory.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Notes
- 1.
The authors would like to acknowledge the fundamental contribution of Dr. Regina Helena da Silva to the development and validation of the PM-DAT.
- 2.
The noise is produced by the horizontal displacement of a piece of metal against a piece of wood.
References
Abílio VC, Freitas FM, Dolnikoff MS, Castrucci AM, Frussa-Filho R. Effects of continuous exposure to light on behavioral dopaminergic supersensitivity. Biol Psychiatry. 1999;45:1622–9.
Agnati LF, Fuxe K, Benfenati F, Batistini N, Zini I, Toffano G. Chronic ganglioside treatment counteracts the biochemical signs of dopamine receptor supersensitivity induced by chronic haloperidol treatment. Neurosci Lett. 1983;40:293–7.
Aporti F, Borsato R, Calderini G, Rubini R, Toffano G, Zanotti A, et al. Age-dependent spontaneous EEG bursts in rats: effects of brain phosphatidylserine. Neurobiol Aging. 1986;7:115–20.
Bellot RG, Camarini R, Vital MA, Palermo-Neto J, Leyton V, Frussa-Filho R. Monosialoganglioside attenuates the excitatory and behavioural sensitization effects of ethanol. Eur J Pharmacol. 1996;313(3):175–9.
Beracochea D. Anterograde and retrograde effects of benzodiazepines on memory. Sci World J. 2006;6:1460–5.
Bonnet MH, Arand DL. We are chronically sleep deprived. Sleep. 1995;18:908–11.
Bonnet MH, Arand DL. Clinical effects of sleep fragmentation versus sleep deprivation. Sleep Med Rev. 2003;7:297–310.
Bouyer JJ, Deminiere W, Mayo W, Le Moal M. Inter-individual differences in the effects of acute stress on the sleep-wakefulness cycle in the rat. Neurosci Lett. 1997;225:193–6.
Bruins Slot LA, Colpaert FC. Opiate states of memory: receptor mechanisms. J Neurosci. 1999;19:10520–9.
Bruins Slot LA, Koek W, Colpaert FC. Ethanol state dependence involving a lever press response requirement in rats. Behav Pharmacol. 1999;10:229–33.
Bueno OF, Lobo LL, Oliveira MG, Gugliano EB, Pomarico AC, Tufik S. Dissociated paradoxical sleep deprivation effects on inhibitory avoidance and conditioned fear. Physiol Behav. 1994;56:775–9.
Calzavara MB, Lopez GB, Abílio VC, Silva RH, Frussa-Filho R. Role of anxiety levels in memory performance of spontaneously hypertensive rats. Behav Pharmacol. 2004;15:545–53.
Carvalho RC, Silva RH, Abílio VC, Barbosa PN, Frussa-Filho R. Antidyskinetic effects of risperidone on animal models of tardive dyskinesia in mice. Brain Res Bull. 2003;60:115–24.
Carvalho RC, Patti CL, Takatsu-Coleman AL, Kameda SR, Souza CF, Garcez-do-Carmo L, et al. Effects of reserpine on the plus-maze discriminative avoidance task: dissociation between memory and motor impairments. Brain Res. 2006;1122:179–83.
Castro JP, Frussa-Filho R, Fukushiro DF, Chinen CC, Abílio VC, Silva RH. Effects of long-term continuous exposure to light on memory and anxiety in mice. Physiol Behav. 2005;86:218–23.
Castro JP, Frussa-Filho R, Fukushiro DF, Silva RH, Medrano WA, Ribeiro RA, et al. Effects of baclofen on reserpine-induced vacuous chewing movements in mice. Brain Res Bull. 2006;68:436–41.
Claro FT, Silva RH, Frussa-Filho R. Bovine brain phosphatidylserine attenuates scopolamine-induced amnesia. Physiol Behav. 1999;67:551–4.
Cochran JC, Thorne DR, Penetar DM, Newhouse PA. Decoupling motor memory strategies: effects of sleep deprivation and amphetamine. Int J Neurosci. 1994;74:45–54.
Cohen C, Perrault G, Sanger DJ. Evidence for the involvement of dopamine receptors in ethanol-induced hyperactivity in mice. Neuropharmacology. 1997;36:1099–108.
Colpaert FC. Pharmacological characteristics of tremor, rigidity and hypokinesia induced by reserpine in rats. Neuropharmacology. 1987;26:1431–40.
Colpaert FC. Amnestic trace locked into the benzodiazepine state of memory. Psychopharmacology (Berl). 1990;102:28–36.
Colpaert FC. System theory of pain and of opiate analgesia: no tolerance to opiates. Pharmacol Rev. 1996;47:605–29.
Colpaert FC, Koek W, Bruins Slot LA. Evidence that amnesic state govern normal and disordered memory. Behav Pharmacol. 2001;12:575–89.
Conceição IM, Maiolini Jr M, Mattia MA, Vital MA, Santos BR, Smaili S, et al. Anxiety-induced antinociception in the mouse. Braz J Med Biol Res. 1992;25:831–4.
Conceição IM, Maioline Jr M, Mattia NF, Chang YH, Smaili S, Frussa-Filho R. Effect of withdrawal from long-term nifedipine administration on open-field habituation in the rat. Braz J Med Biol Res. 1994;27:1363–7.
Cooper JA, Sagar HJ, Jordan N, Harvey NS, Sullivan E. Cognitive impairment in early, untreated Parkinson’s disease and its relationship to motor disability. Brain. 1991;14:2095–122.
Crook T, Petrie W, Wells C, Massari DC. Effects of phosphatidylserine in Alzheimer’s disease. Psychopharmacol Bull. 1992;28:61–6.
Dinges DF, Pack F, Williams K, Gillen KA, Powell JW, Ott GE, et al. Cumulative sleepiness, mood disturbance, and psychomotor vigilance performance decrements during a week of sleep restricted to 4–5 hours per night. Sleep. 1997;20:267–77.
Fluck E, File SE, Springett J, Kopelman MD, Rees J, Orgill J. Does the sedation resulting from sleep deprivation and lorazepam cause similar cognitive deficits? Pharmacol Biochem Behav. 1998;59:909–15.
Frussa-Filho R, Otoboni JR, Uema FT, Sá-Rocha LC. Evaluation of memory and anxiety in rats observed in the elevated plus-maze: effects of age and isolation. Braz J Med Biol Res. 1991;24:725–8.
Frussa-Filho R, Otoboni JR, Gianotti AD, Amaral ACS, Conceição IM. Effects of age on antinociceptive effects of elevated plus-maze exposure. Braz J Med Biol Res. 1992;25:827–9.
Frussa-Filho R, Barbosa-Júnior H, Silva RH, Da Cunha C, Mello CF. Naltrexone potentiates the anxiolytic effects of chlordiazepoxide in rats exposed to novel environments. Psychopharmacology (Berl). 1999;147:168–73.
Goldstone S, Nurnberg HG, Lhamon WT. Effects of trifluoperazine, chlorpromazine, and haloperidol upon temporal information processing by schizophrenic patients. Psychopharmacology (Berl). 1979;65:119–24.
Goto SH, Conceição IM, Ribeiro RA, Frussa-Filho R. Comparison of anxiety measured in the elevated plus-maze, open-field and social interaction tests between spontaneously hypertensive rats and Wistar EPM 1 rats. Braz J Med Biol Res. 1993;26:965–9.
Graeff FG, Vianna MB, Tomaz C. The elevated T-maze, a new experimental model of anxiety and memory: effect of diazepam. Braz J Med Biol Res. 1993;26:67–70.
Handley SL, Mitani S. Effects of alfa-adrenoceptor agonists and antagonists in a maze exploration model of ‘fear’-motivated behavior. Naunyn Schmiedebergs Arch Pharmacol. 1984;327:1–5.
Hanks GW, O’Neill WM, Simpson P, Wesnes K. The cognitive and psychomotor effects of opioid analgesics. II. A randomized controlled trial of single doses of morphine, lorazepam and placebo in healthy subjects. Eur J Clin Pharmacol. 1995;48:455–60.
Hernández OH, Vogel-Sprott M, Ke-Aznar VI. Alcohol impairs the cognitive component of reaction time to an omitted stimulus: a replication and an extension. J Stud Alcohol Drugs. 2007;68:276–81.
Isomae K, Morimoto S, Hasegawa H, Morita K, Kamei J. Effects of T-82, a novel acetylcholinesterase inhibitor, on impaired learning and memory in passive avoidance task in rats. Eur J Pharmacol. 2003;465:97–103.
Itoh J, Nabeshima T, Kameyama T. Utility of an elevated plus-maze for the evaluation of memory in mice: effects of nootropics, scopolamine and electroconvulsive shock. Psychopharmacology (Berl). 1990;101:27–33.
Izquierdo I, Perry ML, Dias RD, Souza DO, Elizabetsky E, Carrasco MA, et al. Endogenous opioids memory modulation and state dependency. In: Martinez JL, Jensen RA, Messing RB, Rigter H, McGaugh JL, editors. Endogenous peptides and learning and memory process. New York: Academic; 1981. p. 269–90.
Jackson A, Koek W, Colpaert FC. NMDA antagonists make learning and recall state-dependent. Behav Pharmacol. 1992;3:415–21.
Kameda SR, Frussa-Filho R, Carvalho RC, Takatsu-Coleman AL, Ricardo VP, Patti CL, et al. Dissociation of the effects of ethanol on memory, anxiety, and motor behavior in mice tested in the plus-maze discriminative avoidance task. Psychopharmacology (Berl). 2007;192:39–48.
Karni A, Tanne D, Rubenstein BS, Askenasy JJ, Sagi D. Dependence on REM sleep of overnight improvement of a perceptual skill. Science. 1994;265:679–82.
Lee C, Rodgers RJ. Antinociceptive effects of elevated plus-maze exposure: influence of opiate receptor manipulations. Psychopharmacology (Berl). 1990;102:507–13.
Levin ED, Wilson W, Rose JE, McEvoy J. Nicotine-haloperidol interactions and cognitive performance in schizophrenics. Neuropsychopharmacology. 1996;15:429–36.
Lister RG. The use of a plus-maze to measure anxiety in the mouse. Psychopharmacology (Berl). 1987;92:180–5.
Martinez Jr JL, Schulteis G, Janak PH, Weinberger SB. Behavioral assessment of forgetting in aged rodents and its relationship to peripheral sympathetic function. Neurobiol Aging. 1988;9:697–708.
Mednick SC, Nakayama K, Cantero JL, Atienza M, Levin AA, Pathak N, Stickgold R. The restorative effect of naps on perceptual deterioration. Nat Neurosci. 2002;5:677–81.
Miceli G, Caltagirone C, Gainotti G. Gangliosides in the treatment of mental deterioration. A double-blind comparison with placebo. Acta Psychiatr Scand. 1997;55:102–10.
Mizumori SJ, Sakai DH, Rosenzweig MR, Bennett EL, Wittreich P. Investigations into the neuropharmacological basis of temporal stages of memory formation in mice trained in an active avoidance task. Behav Brain Res. 1987;23:239–50.
Nunzi MG, Milan F, Guidolin D, Zanotti A, Toffano G. Therapeutic properties of phosphatidylserine in the aging brain. In: Hanin I, Pepeu G, editors. Phospholipids. New York: Plenum Press; 1990. p. 213–8.
Owen AM, James M, Leigh PN, Summers BA, Marsden CD, Quinn NP, et al. Fronto-striatal cognitive deficits at different stages of Parkinson’s disease. Brain. 1992;115:1727–51.
Patti CL, Kameda SR, Carvalho RC, Takatsu-Coleman AL, Lopez GB, Niigaki ST, et al. Effects of morphine on the plus-maze discriminative avoidance task: role of state-dependent learning. Psychopharmacology (Berl). 2006;184:1–12.
Pellow S, Chopin P, File SE, Briley M. Validation of open: closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J Neurosci Methods. 1985;14:149–67.
Pierce RC, Kalivas PW. A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res Brain Res Rev. 1997;25:192–216.
Rahmann H. Brain gangliosides: neuromodulators for synaptic transmission and memory formation. In: Matthies H, editor. Advances in the biosciences. Oxford: Pergamon Press; 1986. p. 235–45.
Ramos A, Kangerski AL, Basso PF, Da Silva Santos JE, Assreuy J, Vendruscolo LF, et al. Evaluation of Lewis and SHR rat strains as a genetic model for the study of anxiety and pain. Behav Brain Res. 2002;129:113–23.
Rapeli P, Kivisaari R, Kähkönen S, Puuskari V, Autti T, Kalska H. Do individuals with former amphetamine dependence have cognitive deficits? Nord J Psychiatry. 2005;59:293–7.
Rapport MM. Introduction to the biochemistry of gangliosides. In: Rapport MM, Gorio A, editors. Gangliosides in neurobiological and neuromuscular function, development and repair. New York: Raven; 1981. p. 15–9.
Rodgers RJ, Lee C, Shepherd JK. Effects of diazepam on behavioural and antinociceptive responses to elevated plus-maze in male mice depend upon treatment regimen and prior maze experience. Psychopharmacology (Berl). 1992;106:102–10.
Rosenzweig MR, Bennett EL, Colombo PJ, Lee DW, Serrano PA. Short-term, intermediate-term, and long-term memories. Behav Brain Res. 1993;5:193–8.
Schreiber S, Kampf-Sherf O, Gorfine M, Kelly D, Oppenheim Y, Lerer B. An open trial of plant-source derived phosphatydilserine for treatment of age-related cognitive decline. Isr J Psychiatry Relat Sci. 2000;37:302–7.
Seifert W, Wierasko A, Terlau H, Hollmann M. Gangliosides and neuronal plasticity in the hippocampus. NATO ASI Ser. 1987;7:523–8.
Siegel JM. The REM, sleep-memory consolidation hypothesis. Science. 2001;294:1058–63.
Silva RH, Frussa-Filho R. The plus-maze discriminative avoidance task: a new model to study memory-anxiety interactions. Effects of chlordiazepoxide and caffeine. J Neurosci Methods. 2000;102:117–25.
Silva RH, Frussa-Filho R. Naltrexone potentiates both amnestic and anxiolytic effects of chlordiazepoxide in mice. Life Sci. 2002;72:721–30.
Silva RH, Bellot RG, Vital MABF, Frussa-Filho R. Effects of long-term ganglioside GM1 administration on a new discriminative avoidance test in normal adult mice. Psychopharmacology (Berl). 1997;129:322–8.
Silva RH, Felicio LF, Frussa-Filho R. Ganglioside GM1 attenuates scopolamine-induced amnesia in rats and mice. Psychopharmacology (Berl). 1999;141:111–7.
Silva RH, Abílio VC, Torres-Leite D, Bergamo M, Chinen CC, Claro FT, et al. Concomitant development of oral dyskinesia and memory deficits in reserpine-treated male and female mice. Behav Brain Res. 2002a;132:171–7.
Silva RH, Kameda SR, Carvalho RC, Rigo GS, Costa KL, Taricano ID, et al. Effects of amphetamine on the plus-maze discriminative avoidance task in mice. Psychopharmacology (Berl). 2002b;160:9–18.
Silva RH, Abílio VC, Takatsu AL, Kameda SR, Grassl C, Chehin AB, et al. Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice. Neuropharmacology. 2004a;46:895–903.
Silva RH, Chehin AB, Kameda SR, Takatsu-Coleman AL, Abílio VC, Tufik S, et al. Effects of pre- or post-training paradoxical sleep deprivation on two animal models of learning and memory in mice. Neurobiol Learn Mem. 2004b;82:90–8.
Smith C, Kelly G. Paradoxical sleep deprivation applied two days after end of training retards learning. Physiol Behav. 1998;43:213–6.
Spanagel R. Modulation of drug-induced sensitization processes by endogenous opioid systems. Behav Brain Res. 1995;70:37–49.
Stip E. Cognition, schizophrenia and the effect of antipsychotics. Encéphale. 2006;32:341–50.
Suchecki D, Duarte-Palma B, Tufik S. Sleep rebound in animals deprived of paradoxical sleep by the modified multiple platform method. Brain Res. 2000;875:14–22.
Sutton MA, Masters SE, Bagnall MW, Carew TJ. Molecular mechanisms underlying a unique intermediate phase of memory in aplysia. Neuron. 2001;31:143–54.
Tettamanti G, Sonnino S, Ghiondi R, Masserini M, Venerando B. Chemical and functional properties of gangliosides. Their possible implication in the membrane mediated transfer of information. In: Degiorgio V, Corti M, editors. Physics and amphiphiles: micelles, vesicles and microemulsions. Amsterdam: North Holland Physics; 1985. p. 607–36. XC Corso Soc Ital Fisica Bologna.
Tipper CM, Cairo TA, Woodward TS, Phillips AG, Liddle PF, Ngan ET. Processing efficiency of a verbal working memory system is modulated by amphetamine: an fMRI investigation. Psychopharmacology (Berl). 2005;180:634–43.
Toffano G, Agnati LF, Fuxe KG. The effect of the ganglioside GM1 on neuronal plasticity. Int J Dev Neurosci. 1986;4:97–100.
Walker MP, Stickgold R. Sleep-dependent learning and memory consolidation. Neuron. 2004;44:121–33.
Youngblood BD, Zhou J, Smagin GN, Ryan DH, Harris RB. Sleep deprivation by the “flower pot” technique and spatial reference memory. Physiol Behav. 1997;61:249–56.
Zanotti A, Valzelli L, Toffano G. Reversal of scopolamine-induced amnesia by phosphatidylserine in rats. Psychopharmacology (Berl). 1986;90:274–5.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this chapter
Cite this chapter
Frussa-Filho, R., de Lima Patti, C., Fukushiro, D.F., Ribeiro, L.T.C., Kameda, S.R., de Cassia Carvalho, R. (2016). The Plus-Maze Discriminative Avoidance Task: An Ethical Rodent Model for Concomitant Evaluation of Learning, Memory, Anxiety, Motor Activity and Their Interactions. In: Andersen, M., Tufik, S. (eds) Rodent Model as Tools in Ethical Biomedical Research. Springer, Cham. https://doi.org/10.1007/978-3-319-11578-8_19
Download citation
DOI: https://doi.org/10.1007/978-3-319-11578-8_19
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-11577-1
Online ISBN: 978-3-319-11578-8
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)