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Effects of prior cocaine self-administration on cognitive performance in female cynomolgus monkeys

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Abstract

Cocaine use has been associated with cognitive impairments that may contribute to poor treatment outcomes. However, the degree to which these deficits extend into periods of abstinence has not been completely elucidated. This study tested whether prior experience self-administering cocaine affected acquisition of two cognitive tasks in 16 adult female cynomolgus monkeys. Seven monkeys had previously self-administered cocaine but had not had access to cocaine for 2 months at the start of this study. After monkeys were trained to respond on a touchscreen, associative learning and behavioral flexibility were assessed using a stimulus discrimination (SD) and reversal (SDR) task from the CANTAB battery. Performance on this task was monitored over the subsequent 3 months. Additionally, working memory was assessed with a delayed match-to-sample (DMS) task. Cocaine-naïve monkeys required fewer total trials and made fewer errors and omissions before acquiring the SD and SDR tasks compared with monkeys who had previously self-administered cocaine; two monkeys in the latter group did not acquire the task. However, this cognitive impairment dissipated over several months of exposure to the task. The number of sessions for touch training and delays required to establish a performance-based curve on the DMS task did not differ between groups. Results suggest that cocaine exposure can impair the ability to learn a novel task requiring behavioral inhibition and flexibility, even after an extended period of abstinence. However, this deficit did not extend to maintenance of the task or to acquisition of a working memory task.

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References

  • Aharonovich E, Hasin DS, Brooks AC, Liu X, Bisaga A, Nunes EV (2006) Cognitive deficits predict low treatment retention in cocaine dependent patients. Drug Alcohol Depend 81:313–322

    Article  PubMed  Google Scholar 

  • Anker JJ, Carroll ME (2011) Females are more vulnerable to drug abuse than males: evidence from preclinical studies and the role of ovarian hormones. Curr Top Behav Neurosci 8:73–96

    Article  CAS  PubMed  Google Scholar 

  • Arnsten AF (1997) Catecholamine regulation of the prefrontal cortex. J Psychopharmacol 11:151–62

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  • Bell RP, Foxe JJ, Ross LA, Garavan H (2013) Intact inhibitory control processes in abstinent drug abusers (I): a functional neuroimaging study in former cocaine addicts. Neuropharmacology. doi: 10.1016/j.neuropharm.2013.02.018

  • Bolla K, Ernst M, Kiehl K, Mouratidis M, Eldreth D, Contoreggi C, Matochik J, Kurian V, Cadet J, Kimes A, Funderburk F, London E (2004) Prefrontal cortical dysfunction in abstinent cocaine abusers. J Neuropsychiatry Clin Neurosci 16:456–464

    Article  PubMed Central  PubMed  Google Scholar 

  • Calu DJ, Stalnaker TA, Franz TM, Singh T, Shaham Y, Schoenbaum G (2007) Withdrawal from cocaine self-administration produces long-lasting deficits in orbitofrontal-dependent reversal learning in rats. Learn Mem 14:325–328

    Article  PubMed Central  PubMed  Google Scholar 

  • Camchong J, MacDonald AW 3rd, Nelson B, Bell C, Mueller BA, Specker S, Lim KO (2011) Frontal hyperconnectivity related to discounting and reversal learning in cocaine subjects. Biol Psychiatry 69:1117–1123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Carroll KM, Kiluk BD, Nich C, Babuscio TA, Brewer JA, Potenza MN, Ball SA, Martino S, Rounsaville BJ, Lejuez CW (2011) Cognitive function and treatment response in a randomized clinical trial of computer-based training in cognitive-behavioral therapy. Subst Use Misuse 46:23–34

    Article  PubMed Central  PubMed  Google Scholar 

  • Connolly CG, Bell RP, Foxe JJ, Garavan H (2013) Dissociated grey matter changes with prolonged addiction and extrnded abstinence in cocaine users. PLoS One 8:359645

    Article  Google Scholar 

  • Cools R, D’Esposito M (2011) Inverted U-shaped dopamine actions on human working memory and cognitive control. Biol Psychiatry 69:e113–e125

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Cotto JH, Davis E, Dowling GJ, Elcano JC, Staton AB, Weiss SR (2010) Gender effects of drug use, abuse and dependence: a special analysis of results form the National Survey on Drug Use and Health. Gend Med 7:402–413

    Article  PubMed  Google Scholar 

  • Czernecki V, Pillon B, Houeto JL, Pochon JB, Levy R, Dubois B (2002) Motivation, reward, and Parkinson's disease: influence of dopatherapy. Neuropsychologia 40:2257–2267

    Article  CAS  PubMed  Google Scholar 

  • Czoty PW, McCabe C, Nader MA (2005) Assessment of the relative reinforcing strength of cocaine in socially housed monkeys using a choice procedure. J Pharmacol Exp Ther 312:96–102

    Article  CAS  PubMed  Google Scholar 

  • De Oliveira LG, Barroso LP, Silveira CM, Sanchez ZV, De Carvalho PJ, Vaz LJ, Nappo SA (2009) Neuropsychological assessment of current and past crack cocaine users. Subst Use Misuse 44:1941–1957

    Article  PubMed  Google Scholar 

  • Di Sclafani V, Tolou-Shams M, Price LJ, Fein G (2002) Neuropsychological performance of individuals dependent on crack-cocaine, or crack-cocaine and alcohol, at 6 weeks and 6 months of abstinence. Drug Alcohol Depend 66:161–171

    Article  PubMed Central  PubMed  Google Scholar 

  • Ersche KD, Roiser JP, Abbott S, Craig KJ, Müller U, Suckling J, Ooi C, Shabbir SS, Clark L, Sahakian BJ, Fineberg NA, Merlo-Pich EV, Robbins TW, Bullmore ET (2011) Response perseveration in stimulant dependence is associated with striatal dysfunction and can be ameliorated by a D(2/3) receptor agonist. Biol Psychiatry 70:754–762

    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  PubMed Central  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 

  • Fletcher PJ, Tenn CC, Sinyard J, Rizos Z, Kapur S (2007) A sensitizing regimen of amphetamine impairs visual attention in the 5-choice serial reaction time test: reversal by a D1 receptor agonist injected into the medial prefrontal cortex. Neuropsychopharmacology 32:1122–1132

    Article  CAS  PubMed  Google Scholar 

  • Gould RW, Gage HD, Nader MA (2012) Effects of chronic cocaine self-administration on cognition and cerebral glucose utilization in rhesus monkeys. Biol Psychiatry 72:856–863

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Greenfield SF, Trucco EM, McHugh RK, Lincoln M, Gallop RJ (2007) The Women's Recovery Group Study: a Stage I trial of women-focused group therapy for substance use disorders versus mixed-gender group drug counseling. Drug Alcohol Depend 90:39–47

    Article  PubMed Central  PubMed  Google Scholar 

  • Hanlon CA, Dufault DL, Wesley MJ, Porrino LJ (2011) Elevated gray and white matter densities in cocaine abstainers compared to current users. Psychopharmacology 218:681–692

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Hyman SM, Paliwal P, Chaplin TM, Mazure CM, Rounsaville BJ, Sinha R (2008) Severity of childhood trauma is predictive on cocaine relapse outcomes in women but not men. Drug Alcohol Depend 92:208–216

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Jentsch JD, Olausson P, De La Garza R 2nd, Taylor JR (2002) Impairments of reversal learning and response perseveration after repeated, intermittent cocaine administrations to monkeys. Neuropsychopharmacology 26:183–190

    Article  CAS  PubMed  Google Scholar 

  • Jovanovski D, Erb S, Zakzanis KK (2005) Neurocognitive deficits in cocaine users: a quantitative review of the evidence. J Clin Exp Neuropsychol 27:189–204

    Article  PubMed  Google Scholar 

  • Kangas BD, Bergman J (2014) Repeated acquisition and discrimination reversal in the squirrel monkey (Saimiri sciureus). Anim Cogn 17:221–228

    Article  PubMed Central  PubMed  Google Scholar 

  • Krueger DD, Howell JL, Oo H, Olausson P, Taylor JR, Nairn AC (2009) Prior chronic cocaine exposure in mice induces persistent alterations in cognitive function. Behav Pharmacol 20:695–704

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Liu S, Heitz RP, Sampson AR, Zhang W, Bradberry CW (2008) Evidence of temporal cortical dysfunction in rhesus monkeys following chronic cocaine self-administration. Cereb Cortex 18:2109–2116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Lynch WJ, Carroll ME (2000) Reinstatement of cocaine self-administration in rats: sex differences. Psychopharmacology 148:196–2000

    Article  CAS  PubMed  Google Scholar 

  • Lynch WJ, Carroll ME (1999) Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats. Psychopharmacology 144:77–82

    Article  CAS  PubMed  Google Scholar 

  • Lynch WJ, Taylor JR (2005) Decreased motivation following cocaine self-administration under extended access conditions: effects of sex and ovarian hormones. Neuropsychopharmacology 30:927–935

    Article  CAS  PubMed  Google Scholar 

  • Moeller SJ, Tomasi D, Honorio J, Volkow ND, Goldstein RZ (2012) Dopaminergic involvement during mental fatigue in health and cocaine addiction. Transl Psychiatry 2:e176

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Morie KP, Garavan H, Bell RP, De Sanctis P, Krakowski MI, Foxe JJ (2013) Intact inhibitory control processes in abstinent drug abusers (II): a high-density electrical mapping study in former cocaine and heroin addicts. Neuropharmacology. doi: 10.1016/j.neuropharm.2013.02.023

  • Nader MA, Morgan D, Gage HD, Nader SH, Calhoun TL, Bucjhheimer N, Ehrenkaufer R, Mach RH (2006) PET imaging of dopamine D2 receptors during chronic cocaine self-administration in monkeys. Nat Neurosci 9:1050–1056

    Article  CAS  PubMed  Google Scholar 

  • Nakamura K, Kurasawa M, Tanaka Y (1998) Apomorphine-induced hypo-attention in rats and reversal of the choice performance impairment by aniracetam. Eur J Pharmacol 342:127–138

    Article  CAS  PubMed  Google Scholar 

  • Nandam LS, Hester R, Wagner J, Dean AJ, Messer C, Honeysett A, Nathan PJ, Bellgrove MA (2013) Dopamine D2 receptor modulation of human response inhibition and error awareness. J Cogn Neurosci 25:649–656

    Article  PubMed  Google Scholar 

  • O'Brien MS, Anthony JC (2005) Risk of becoming cocaine dependent: epidemiological estimates for the United States, 2000–2001. Neuropsychopharmacology 30:1006–1018

    Article  PubMed  Google Scholar 

  • Oscar-Berman M, Marinković K (2007) Alcohol: effects on neurobehavioral functions and the brain. Neuropsychol Rev 17:239–257

    Article  PubMed Central  PubMed  Google Scholar 

  • Pace-Schott EF, Morgan PT, Malison RT, Hart CL, Edgar C, Walker M, Stickgold R (2008) Cocaine users differ from normals on cognitive tasks which show poorer performance during drug abstinence. Am J Drug Alcohol Abuse 34:109–121

    Article  PubMed  Google Scholar 

  • Porter JN, Gurnsey K, Jedema HP, Bradberry CW (2013) Latent vulnerability in cognitive performance following chronic self-administration in rhesus monkeys. Psychopharmacology 226:139–146

  • Porter JN, Minhas D, Lopresti BJ, Price JC, Bradberry CW (2014) Altered cerebellar and prefrontal cortex function in rhesus monkeys that previously self-administered cocaine. Psychopharmacol 231:4211–4218

    Article  CAS  Google Scholar 

  • Porter JN, Olsen AS, Gurnsey K, Dugan BP, Jedema HP, Bradberry CW (2011) Chronic cocaine self-administration in rhesus monkeys: impact on associative learning, cognitive control, and working memory. J Neurosci 31:4926–4934

    Article  PubMed Central  CAS  PubMed  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 

  • Siqueland L, Crits-Christoph P, Gallop R, Berber JP, Griffin ML, Thase ME, Daley D, Frank A, Gastfriend DR, Blaine J, Connolly MB, Gladis M (2002) Retention in psychosocial treatment of cocaine dependence: predictors and impact on outcome. Am J Addict 11:24–40

    Article  PubMed  Google Scholar 

  • Sofuoglu M, DeVito EE, Waters AJ, Carroll KM (2013) Cognitive enhancement as a treatment for drug addictions. Neuropharmacology 64:452–463

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Spronk DB, van Wel JH, Ramaekers JG, Verkes RJ (2013) Characterizing the cognitive effects of cocaine: a comprehensive review. Neurosci Biobehav Rev 37:1838–1859

    Article  CAS  PubMed  Google Scholar 

  • SAMHSA (Substance Abuse and Mental Health Services Administration) (2013) Results from the 2012 National Survey on Drug Use and Health: Volume I. Summary of National Findings (NSDUH Series H-46, HHS Publication No. (SMA) 13-4795. Substance Abuse and Mental Health Services Administration, U.S. Dept. of Health and Human Services, Rockville, MD

  • Taffe MA, Weed MR, Davis S, Huitron-Resendiz S, Schroeder R, Parson SLH, Henriksen SJ, Gold LH (2001) Functional consequences of repeated (+/−)3,4-methylenedioxymethamphetamine (MDMA) treatment in rhesus monkeys. Neuropsychopharmacology 24:230–239

    Article  CAS  PubMed  Google Scholar 

  • Teichner G, Horner MD, Roitzsch JC, Herron J, Thevos A (2002) Substance abuse treatment outcomes for cognitively impaired and intact outpatients. Addict Behav 27:751–763

    Article  PubMed  Google Scholar 

  • Tomasi D, Goldstein RZ, Telang F, Maloney T, Alia-Klein N, Caparelli EC, Volkow ND (2007) Widespread disruption in brain activation patterns to a working memory task during cocaine abstinence. Brain Res 1171:83–92

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Tranel D, Damasio H, Denburg NL, Bechara A (2005) Does gender play a role in functional asymmetry of ventromedial prefrontal cortex? Brain 128:2872–2881

    Article  PubMed  Google Scholar 

  • van der Plas EA, Crone EA, van den Wildenberg WP, Tranel D, Bechara A (2009) Executive control deficits in substance-dependent individuals: a comparison of alcohol, cocaine, and methamphetamine in men and women. J Clin Exp Neuropsychol 31:706–719

    Article  PubMed Central  PubMed  Google Scholar 

  • van Holst RJ, Schilt T (2011) Drug-related decrease in neuropsychological functions of abstinent drug users. Curr Drug Abuse Rev 4:42–56

    Article  PubMed  Google Scholar 

  • Verdejo-García A, Bechara A, Recknor EC, Pérez-García M (2006) Executive dysfunction in substance dependent individuals during drug use and abstinence: an examination of the behavioral, cognitive and emotional correlates of addiction. J Int Neuropsychol Soc 12:405–415

    PubMed  Google Scholar 

  • Verdejo-García A, López-Torrecillas F, Giménez CO, Pérez-García M (2004) Clinical implications and methodological challenges in the study of the neuropsychological correlates of cannabis, stimulant, and opioid abuse. Neuropsychol Rev 14:1–41

    Article  PubMed  Google Scholar 

  • Verdejo-García AJ, Perales JC, Pérez-García M (2007) Cognitive impulsivity in cocaine and heroin polysubstance abusers. Addict Behav 32:950–966

    Article  PubMed  Google Scholar 

  • Verrico CD, Haile CN, Newton TF, Kosten TR, De La Garza R (2013) Pharmacotherapeutics for substance-use disorders: a focus on dopaminergic medications. Expert Opin Investig Drugs 22:1549–1568

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  • Volkow ND, Hitzemann R, Wang GJ, Fowler JS, Wolf AP, Dewey SL, Handlesman L (1992) Long-term frontal brain metabolic changes in cocaine abusers. Synapse 11:184–190

    Article  CAS  PubMed  Google Scholar 

  • Weed MR, Taffe MA, Polis I, Roberts AC, Robbins TW, Koob GF, Bloom FE, Gold LH (1999) Performance norms for a rhesus monkey neuropsychological testing battery: acquisition and long-term performance. Brain Res Cogn Brain Res 8:185–201

    Article  CAS  PubMed  Google Scholar 

  • Wood S, Sage JR, Shuman T, Anagnostaras (2013) Psychostimulants and cognition: a continuum of behavioral and cognitive activation. Pharmacol Rev 66:193–221

    Article  PubMed  Google Scholar 

  • Wright MJ Jr, Glavis-Bloom C, Taffe MA (2013) Acute ethanol reduces reversal cost in discrimination learning by reducing perseverance in adolescent rhesus macaques. Alcohol Clin Exp Res 37:952–960

    Article  CAS  PubMed  Google Scholar 

  • Zilberman ML, Hochgraf PB, Andrade AG (2003) Gender differences in treatment-seeking Brazilian drug-dependent individuals. Subst Abus 24:17–25

    PubMed  Google Scholar 

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Acknowledgments

This study was supported by Public Health Service grants DA 007246, DA 29178, DA 17763, and DA 10584.

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Correspondence to Paul W. Czoty.

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Kromrey, S.A., Gould, R.W., Nader, M.A. et al. Effects of prior cocaine self-administration on cognitive performance in female cynomolgus monkeys. Psychopharmacology 232, 2007–2016 (2015). https://doi.org/10.1007/s00213-015-3865-6

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