Skip to main content
Log in

Drugs of abuse as memory modulators: a study of cocaine in rats

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

It has been proposed that drugs of abuse reinforce behavior partly, or wholly, because they facilitate learning by enhancing memory consolidation. Cocaine can clearly serve as a reinforcer, but its effect on learning has not been fully characterized.

Objectives

To explore the effects of different regimens of pre- and post-training cocaine administration on win-stay and object learning.

Methods

Cocaine naïve and cocaine pre-exposed (30 mg/kg/day, ×5 days followed by 7 days drug-free) male Sprague-Dawley rats received cocaine (0, 1, 2.5, 7.5, or 20 mg/kg, i.p.) immediately following training on a win-stay task in a radial maze or following the sample phase of an object learning task. Win-stay performance was also assessed in tests of extinction and after a set shift.

Results

Post-training cocaine did not improve accuracy on the win-stay task and produced performance deficits at 20 mg/kg. These deficits were attenuated by prior cocaine exposure. There was indirect evidence of facilitated learning in extinction and set shift tests, but the effective dosage was different (2.5 and 7.5 mg/kg, respectively). Post-training cocaine produced dose-dependent improvements in object learning.

Conclusion

Post-training cocaine administration can facilitate learning, but this effect is highly dependent on the dose and the type of task employed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Allen CP, Leri F (2010) Effect of acute and repeated cocaine exposure on response matching capabilities of Sprague-Dawley rats responding for sucrose on concurrent schedules of reinforcement. Pharmacol Biochem Behav 96:96–103

    Article  CAS  PubMed  Google Scholar 

  • Arroyo M, Markou A, Robbins TW, Everitt B (1998) Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine. Psychopharmacology 140:331–344

    Article  CAS  PubMed  Google Scholar 

  • Balderas I, Moreno-Castilla P, Bermudez-Rattoni F (2013) Dopamine D1 receptor activity modulates object recognition memory consolidation in the perirhinal cortex but not in the hippocampus. Hippocampus. doi:10.1002/hipo.22143

    PubMed  Google Scholar 

  • Balderas I, Rodriguez-Ortiz CJ, Salgado-Tonda P, Chavez-Hurtado J, McGaugh JL, Bermudez-Rattoni F (2008) The consolidation of object and context recognition memory involve different regions of the temporal lobe. Learn Mem 15:618–624

    Article  PubMed Central  PubMed  Google Scholar 

  • Bardo MT, Rowlett JK, Harris M (1995) Conditioned place preference using opiate and stimulant drugs: a meta-analysis. Neurosci Biobehav Rev 19:39–51

    Article  CAS  PubMed  Google Scholar 

  • Brown MW, Barker GR, Aggleton JP, Warburton EC (2012) What pharmacological interventions indicate concerning the role of the perirhinal cortex in recognition memory. Neuropsychologia 50:3122–3140

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cahill L, McGaugh JL (1990) Amygdaloid complex lesions differentially affect retention of tasks using appetitive and aversive reinforcement. Behav Neurosci 104:532–543

    Article  CAS  PubMed  Google Scholar 

  • Cappell H, LeBlanc AE (1975) Modification of the punishing effects of psychoactive drugs in rats by previous drug experience. J Comp Physiol Psychol 89:347–356

    Article  CAS  PubMed  Google Scholar 

  • Castellano C, Zocchi A, Cabib S, Puglisi-Allegra S (1996) Strain-dependent effects of cocaine on memory storage improvement induced by post-training physostigmine. Psychopharmacology 123:340–345

    Article  CAS  PubMed  Google Scholar 

  • Cloke JM, Rkieh N, Leri F (2013) Effect of post-training administration of cocaine, diazepam and their combination on a win-stay task. Pharmacol Biochem Behav, Nov 15;116C:69-74. doi:10.1016/j.pbb.2013.11.010

  • da Silveira CK, Furini CR, Benetti F, Monteiro C, Izquierdo I (2013) The role of histamine receptors in the consolidation of object recognition memory. Neurobiol Learn Mem 103:64–71

    Article  PubMed  Google Scholar 

  • de Lima MN, Presti-Torres J, Dornelles A, Scalco FS, Roesler R, Garcia VA, Schroder N (2011) Modulatory influence of dopamine receptors on consolidation of object recognition memory. Neurobiol Learn Mem 95:305–310

    Article  PubMed  Google Scholar 

  • Dornelles A, de Lima MN, Grazziotin M, Presti-Torres J, Garcia VA, Scalco FS, Roesler R, Schroder N (2007) Adrenergic enhancement of consolidation of object recognition memory. Neurobiol Learn Mem 88:137–142

    Article  CAS  PubMed  Google Scholar 

  • Ersche KD, Roiser JP, Robbins TW, Sahakian BJ (2008) Chronic cocaine but not chronic amphetamine use is associated with perseverative responding in humans. Psychopharmacology 197:421–431

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ettenberg A, Geist TD (1991) Animal model for investigating the anxiogenic effects of self-administered cocaine. Psychopharmacology 103:455–461

    Article  CAS  PubMed  Google Scholar 

  • Fillmore MT, Rush CR (2006) Polydrug abusers display impaired discrimination-reversal learning in a model of behavioural control. J Psychopharmacol 20:24–32

    Article  PubMed  Google Scholar 

  • Foltin RW, Christiansen I, Levin FR, Fischman MW (1995) Effect of single and multiple intravenous cocaine injections in humans maintained on methadone. J Pharmacol Exp Ther 275:38–47

    CAS  PubMed  Google Scholar 

  • Freeman KB, Riley AL (2005) Cocaine-induced conditioned taste avoidance over extended conditioned stimulus-unconditioned stimulus intervals. Behav Pharmacol 16:591–595

    Article  CAS  PubMed  Google Scholar 

  • Furinini CR, Rossato JI, Bitencourt LL, Medina JH, Izquierdo I, Cammarota M (2010) Beta-adrenergic receptors link NO/sGC/PKG signaling to BDNF expression during the consolidation of object recognition long-term memory. Hippocampus 20:672–683

    Google Scholar 

  • Galuska CM, Woods JH (2005) Acquisition of cocaine self-administration with unsignaled delayed reinforcement in rhesus monkeys. J Exp Anal Behav 84:269–280

    Article  PubMed Central  PubMed  Google Scholar 

  • Goudie AJ, Dickins DW, Thornton EW (1978) Cocaine-induced conditioned taste aversions in rats. Pharmacol Biochem Behav 8:757–761

    Article  CAS  PubMed  Google Scholar 

  • Goulart BK, de Lima MN, de Farias CB, Reolon GK, Almeida VR, Quevedo J, Kapczinski F, Schroder N, Roesler R (2010) Ketamine impairs recognition memory consolidation and prevents learning-induced increase in hippocampal brain-derived neurotrophic factor levels. Neuroscience 167:969–973

    Article  CAS  PubMed  Google Scholar 

  • Grigson PS (1997) Conditioned taste aversions and drugs of abuse: a reinterpretation. Behav Neurosci 111:129–136

    Article  CAS  PubMed  Google Scholar 

  • Hull C (1943) Principles of behavior: An introduction to behavior theory. Appleton-Century-Crofts, New York

    Google Scholar 

  • Hunt T, Amit Z (1986) Conditioned taste aversion induced by self-administered drugs: paradox revisited. Neurosci Biobehav Rev 11:107–130

    Article  Google Scholar 

  • Huston JP, Mueller C, Mondadori C (1977) Memory facilitation by posttrial hypothalamic stimulation and other reinforcers: a central theory of reinforcement. Neurosci Biobehav Rev 1:143–150

    Article  Google Scholar 

  • Huston JP, Oitzl MS (1989) The relationship between reinforcement and memory: parallels in the rewarding and mnemonic effects of the neuropeptide substance P. Neurosci Biobehav Rev 13:171–180

    Article  CAS  PubMed  Google Scholar 

  • Ill-Raga G, Kohler C, Radiske A, Lima RH, Rosen MD, Munoz FJ, Cammarota M (2013) Consolidation of object recognition memory requires HRI kinase-dependent phosphorylation of eIF2a in the hippocampus. Hippocampus 6:431–436

    Article  Google Scholar 

  • Inagaki T, Gautreaux C, Luine V (2010) Acute estrogen treatment facilitates recognition memory consolidation and alters monoamine levels in memory-related brain areas. Horm Behav 58:415–426

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Iniguez SD, Charntikov S, Baella SA, Herbert MS, Bolanos-Guzman CA, Crawford CA (2012) Post-training cocaine exposure facilitates spatial memory consolidation in C7BL/6 mice. Hippocampus 22:802–813

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Introini-Collison IB, McGaugh JL (1989) Cocaine enhances memory storage in mice. Psychopharmacology 99:537–541

    Article  CAS  PubMed  Google Scholar 

  • Janak PH, Keppel G, Martinez JL Jr (1992) Cocaine enhances retention of avoidance conditioning in rats. Psychopharmacology 106:383–387

    Article  CAS  PubMed  Google Scholar 

  • Koob GF, Le Moal M (2006) Neurobiology of addiction. Academic, London

    Google Scholar 

  • Leri F, Nahas E, Henderson K, Limebeer CL, Parker LA, White NM (2013) Effects of post-training heroin and d-amphetamine on consolidation of win-stay learning and fear conditioning. J Neuropsychopharmacol 27:292–301

    Google Scholar 

  • Leri F, Zhou Y, Goddard B, Cummins E, Kreek MJ (2006) Effects of high-dose methadone maintenance on cocaine place conditioning, cocaine self-administration, and mu-opioid receptors mRNA expression in the rat brain. Neuropsychopharmacology 31:1462–1474

    Article  CAS  PubMed  Google Scholar 

  • Lima RH, Rossato JI, Furini CR, Bevilaqua LR, Izquierdo I, Cammarota M (2009) Infusion of protein synthesis inhibitors in the entorhinal cortex blocks consolidation but not reconsolidation of object recognition memory. Neurobiol Learn Mem 91:466–472

    Article  CAS  PubMed  Google Scholar 

  • MacPhail RC (1982) Studies on the flavor aversions induced by trialkyltin compounds. Neurobehav Toxicol Teratol 4:225–230

    CAS  PubMed  Google Scholar 

  • Mayer LA, Parker LA (1993) Rewarding and aversive properties of IP and SC cocaine: assessment by place and taste conditioning. Psychopharmacology 112:189–194

    Article  CAS  PubMed  Google Scholar 

  • McGaugh JL (1966) Time-dependent processes in memory storage. Science 153:1352–1358

    Article  Google Scholar 

  • McGaugh JL (2000) Memory—a century of consolidation. Science 287:348–351

    Article  Google Scholar 

  • Mello-Carpes PB, Izquierdo I (2013) The nucleus of the solitary tract ->nucleus paragigantocellularis ->locus coeruleus ->CA1 region of dorsal hippocampus pathway is important for consolidation of object recognition memory. Neurobiol Learn Mem 100:56–63

    Article  CAS  PubMed  Google Scholar 

  • Olmstead MC, Parkinson JA, Miles FJ, Everitt BJ, Dickinson A (2000) Cocaine-seeking by rats: regulation, reinforcement and activation. Psychopharmacology 152:123–131

    Article  CAS  PubMed  Google Scholar 

  • Packard MG, White NM (1989) Memory facilitation produced by dopamine agonists: role of receptor subtype and mnemonic requirements. Pharmacol Biochem Behav 33:511–518

    Article  CAS  PubMed  Google Scholar 

  • Parker LA (1984) Behavioral conditioned responses across multiple conditioning/testing trials elicited by lithium- and amphetamine-paired flavors. Behav Neural Biol 41:190–199

    Article  CAS  PubMed  Google Scholar 

  • Parker LA (1993) Taste reactivity responses elicited by cocaine-, phencyclidine- and methamphetamine-paired sucrose solutions. Behav Neurosci 107:118–129

    Article  CAS  PubMed  Google Scholar 

  • Parker LA (1995) Rewarding drugs produce taste avoidance, but not taste aversion. Neurosci Biobehav Rev 19:143–157

    Article  CAS  PubMed  Google Scholar 

  • Parker LA (2003) Taste avoidance and taste aversion: evidence for two different processes. Learn Behav 31:165–172

    Article  PubMed  Google Scholar 

  • Puglisi-Allegra S, Cestari V, Cabib C, Castellano C (1994) Strain-dependent effects of post-training cocaine or nomifensine on memory storage involve both D1 and D2 dopamine receptors. Psychopharmacology 115:157–162

    Article  CAS  PubMed  Google Scholar 

  • Reichel CM, Wilkinson JL, Bevins RA (2010) Reference place conditioning procedure with cocaine: increased sensitivity for measuring associatively motivated choice behavior in rats. Behav Pharmacol 21:323–331

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Reicher M, Holman E (1977) Location preference and flavor aversion reinforced by amphetamine in rats. Anim Learn Behav 5:343–346

    Article  Google Scholar 

  • Riley AL, Diamond HF (1998) The effects of cocaine preexposure on the acquisition of cocaine-induced taste aversions. Pharmacol Biochem Behav 60:739–745

    Article  CAS  PubMed  Google Scholar 

  • Rogerio R, Takahashi RN (1992) Anxiogenic properties of cocaine in the rat evaluated with the elevated plus-maze. Pharmacol Biochem Behav 43:631–633

    Article  CAS  PubMed  Google Scholar 

  • Roozendaal B, Castello NA, Vedana G, Barsegyan A, McGaugh JL (2008a) Noradrenergic activation of the basolateral amygdala modulates consolidation of object recognition memory. Neurobiol Learn Mem 90:576–579

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Roozendaal B, Castello NA, Vedana G, Barsegyan A, McGaugh JL (2008b) Noradrenergic activation of the basolateral amygdala modulates consolidation of object recognition memory. Neurobiol Learn Mem 90:576–579

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Rossato JI, Radiske A, Kohler CA, Gonzalez C, Bevilaqua LR, Medina JH, Cammarota M (2013) Consolidation of object recognition memory requires simultaneous activation of dopamine D(1)/D(5) receptors in the amygdala and medial prefrontal cortex but not in the hippocampus. Neurobiol Learn Mem 24:66–70

    Article  Google Scholar 

  • Schoenbaum G, Saddoris MP, Ramus SJ, Shaham Y, Setlow B (2004) Cocaine-experienced rats exhibit learning deficits in a task sensitive to orbitofrontal cortex lesions. Eur J Neurosci 19:1997–2002

    Article  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 102:269274

    Article  Google Scholar 

  • Simon NW, Setlow B (2006) Post-training amphetamine administration enhances memory consolidation in appetitive Pavlovian conditioning: implications for drug addiction. Neurobiol Learn Mem 86:305–310

    Article  CAS  PubMed  Google Scholar 

  • Stalnaker TA, Roesch MR, Franz TM, Burke KA, Schoenbaum G (2006) Abnormal associative encoding in orbitofrontal neurons in cocaine-experienced rats during decision-making. Eur J Neurosci 24:2643–2653

    Article  PubMed Central  PubMed  Google Scholar 

  • Thomsen M, Caine SB (2006) Cocaine self-administration under fixed and progressive ration reinforcement: comparison of C57BL/6 J, 129X1/SvJ, and129S6/SvEvTac inbred mice. Psychopharmacology 184:145–154

    Article  CAS  PubMed  Google Scholar 

  • Underwood BJ (1957) Interference and forgetting. Psychol Rev 64:49–60

    Article  CAS  PubMed  Google Scholar 

  • White NM (1996) Addictive drugs as reinforcers: multiple partial actions on memory systems. Addiction 91:921–949

    Article  CAS  PubMed  Google Scholar 

  • White NM, Milner PM (1992) The psychobiology of reinforcers. Ann Rev Psychol 43:443–471

    Article  CAS  Google Scholar 

  • Wiig KA, Whitlock JR, Epstein MH, Carpenter RL, Bear MF (2009) The levo enantiomer of amphetamine increases memory consolidation and gene expression in the hippocampus without producing locomotor stimulation. Neurobiol Learn Mem 92:106–113

    Article  CAS  PubMed  Google Scholar 

  • Winters BD, Bussey TJ (2005) Transient inactivation of perirhinal cortex disrupts encoding, retrieval, and consolidation of object recognition memory. J Neurosci 25:52–61

    Article  CAS  PubMed  Google Scholar 

  • Wixted JT (2004) The psychology and neuroscience of forgetting. Annu Rev Psychol 55:235–269

    Article  PubMed  Google Scholar 

  • Yang XM, Gorman AL, Dunn AJ, Goeders NE (1992) Neurochemical and behavioral studies. Pharmacol Biochem Behav 41:643–650

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

These studies are funded by the Natural Sciences and Research Council of Canada (NSERC).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francesco Leri.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rkieh, N., Cloke, J.M., Gallagher, N. et al. Drugs of abuse as memory modulators: a study of cocaine in rats. Psychopharmacology 231, 2339–2348 (2014). https://doi.org/10.1007/s00213-013-3390-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-013-3390-4

Keywords

Navigation