Abstract
Rationale
Male rats escalate methamphetamine (meth) intake during long-access meth self-administration, show enhanced reinstatement of meth-seeking, and exhibit meth-induced memory impairments. However, the impact of long-access daily meth self-administration on reinstatement and cognitive dysfunction has not been assessed in females, even though clinical studies on meth addiction have shown differences between men and women.
Objectives
This study determined whether male and freely cycling female rats: (1) escalate meth intake in a 6-h daily-access period relative to 1-h access; (2) show different sensitivity to meth primed reinstatement after short- and long-access conditions; and (3) show deficits in novel object and object in place recognition memory.
Methods
Male and female Long–Evans rats self-administered meth in limited (1-h/day) or extended (6-h/day) daily access sessions. After 21 days, meth access was discontinued, and rats entered an abstinence period. On the seventh and 14th days of abstinence, rats were assessed for recognition memory using tests for: (a) novel object recognition memory and (b) object-in-place memory. Rats were tested for reinstatement of meth-seeking following extinction of responding.
Results
Female rats self-administered more meth and escalated intake faster than males during extended, but not limited, daily access. Both males and females in the extended, but not limited, access groups showed memory deficits on both tasks. Female rats showed greater reinstatement to meth-seeking with lower doses of meth priming injections than males.
Conclusions
Relative to males, females were equally susceptible to meth-induced memory deficits but exhibited higher meth intake and greater relapse to meth-seeking.
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References
Ahmed SH, Koob GF (1999) Long-lasting increase in the set point for cocaine self-administration after escalation in rats. Psychopharmacology 146:303–312
Ahmed SH, Walker JR, Koob GF (2000) Persistent increase in the motivation to take heroin in rats with a history of drug escalation. Neuropsychopharmacology 22:413–421
Berlyne DE (1950) Novelty and curiosity as determinants of exploratory behaviour. Br J Psychol 41:68–80
Brecht M-L, O’Brien A, von Mayrhauser C, Anglin MD (2004) Methamphetamine use behaviors and gender differences. Addict Behav 29:89–106
Caine SB, Bowen CA, Yu G, Zuzga D, Negus SS, Mello NK (2004) Effect of gonadectomy and gonadal hormone replacement on cocaine self-administration in female and male rats. Neuropsychopharmacology 29:929–942
Dalley JW, Theobald DE, Berry D, Milstein JA, Lääne K, Everitt BJ, Robbins TW (2005) Cognitive sequelae of intravenous amphetamine self-administration in rats: evidence for selective effects on attentional performance. Neuropsychopharmacology 30:525–537
Dickerson BC, Eichenbaum H (2010) The episodic memory system: neurocircuitry and disorders. Neuropsychopharmacology 35:86–104
Dluzen DE, Liu B (2008) Gender differences in methamphetamine use and responses: a review. Gend Med 5:24–35
Ennaceur A (2010) One-trial object recognition in rats and mice: methodological and theoretical issues. Behav Brain Res 215:244–254
Ennaceur A, Michalikova S, Bradford A, Ahmed S (2005) Detailed analysis of the behavior of Lister and Wistar rats in anxiety, object recognition and object location tasks. Behav Brain Res 159:247–266
Feltenstein MW, See RE (2007) Plasma progesterone levels and cocaine-seeking in freely cycling female rats across the estrous cycle. Drug Alcohol Depend 89:183–189
Feltenstein MW, Byrd EA, Henderson AR, See RE (2009) Attenuation of cocaine-seeking by progesterone treatment in female rats. Psychoneuroendocrinology 34:343–352
Feltenstein MW, Ghee SM, See RE (2012) Nicotine self-administration and reinstatement of nicotine-seeking in male and female rats. Drug Alcohol Depend 121:240–246
Fuchs RA, Evans KA, Mehta RH, Case JM, See RE (2005) Influence of sex and estrous cyclicity on conditioned cue-induced reinstatement of cocaine-seeking behavior in rats. Psychopharmacology 179:662–672
Hadamitzky M, Markou A, Kuczenski R (2011) Extended access to methamphetamine self-administration affects sensorimotor gating in rats. Behav Brain Res 217:386–390
Haney M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Social stress increases the acquisition of cocaine self-administration in male and female rats. Brain Res 698:46–52
Holtz NA, Lozama A, Prisinzano TE, Carroll ME (2011) Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone. Drug Alcohol Depend 120:233–237
Hser YI, Evans E, Huang YC (2005) Treatment outcomes among women and men methamphetamine abusers in California. J Subst Abus Treat 28:77–85
Hu M, Crombag HS, Robinson TE, Becker JB (2004) Biological basis of sex differences in the propensity to self-administer cocaine. Neuropsychopharmacology 29:81–85
Kippin TE, Fuchs RA, Mehta RH, Case JM, Parker MP, Bimonte-Nelson HA, See RE (2005) Potentiation of cocaine-primed reinstatement of drug seeking in female rats during estrus. Psychopharmacology 182:245–252
Kitamura O, Wee S, Specio S, Koob G, Pulvirenti L (2006) Escalation of methamphetamine self-administration in rats: a dose-effect function. Psychopharmacology 186:48–53
Kosten TA, Sanchez H, Zhang XY, Kehoe P (2004) Neonatal isolation enhances acquisition of cocaine self-administration and food responding in female rats. Behav Brain Res 151:137–149
Kucerova J, Vrskova D, Sulcova A (2009) Impact of repeated methamphetamine pretreatment on intravenous self-administration of the drug in males and estrogenized or non- estrogenized ovariectomized female rats. Neuro Endocrinol Lett 30:663–670
Lynch WJ, Carroll ME (1999) Sex differences in the acquisition of intravenously self-administered cocaine and heroin in rats. Psychopharmacology 144:77–82
Lynch WJ, Carroll ME (2000) Reinstatement of cocaine self-administration in rats: sex differences. Psychopharmacology 148:196–200
Lynch WJ, Taylor JR (2004) Sex differences in the behavioral effects of 24-h/day access to cocaine under a discrete trial procedure. Neuropsychopharmacology 29:943–951
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
Lynch WJ, Arizzi MN, Carroll ME (2000) Effects of sex and the estrous cycle on regulation of intravenously self-administered cocaine in rats. Psychopharmacology 152:132–139
Marcondes FK, Bianchi FJ, Tanno AP (2002) Determination of the estrous cycle phases of rats: some helpful considerations. Braz J Biol 62:609–614
Markou A, Weiss F, Gold L, Caine S, Schulteis G, Koob G (1993) Animal models of drug craving. Psychopharmacology 112:163–182
Milesi-Hallé A, McMillan DE, Laurenzana EM, Byrnes-Blake KA, Owens SM (2007) Sex differences in (+)-amphetamine- and (+)-methamphetamine-induced behavioral response in male and female Sprague–Dawley rats. Pharmacol Biochem Behav 86:140–149
National Research Council (1996) Guide for the care and use of laboratory animals. National Academy Press, Washington, DC
Paris JJ, Frye CA (2008) Estrous cycle, pregnancy, and parity enhance performance of rats in object recognition or object placement tasks. Reproduction 136:105–115
Parsegian A, Glen WB, Lavin A, See RE (2011) Methamphetamine self-administration produces attentional set-shifting deficits and alters prefrontal cortical neurophysiology in rats. Biol Psychiatry 69:253–259
Paterson NE, Markou A (2003) Increased motivation for self-administered cocaine after escalated cocaine intake. Neuroreport 14:2229–2232
Rawson R, Gonzales R, Obert JL, McCann MJ, Brethen P (2005) Methamphetamine use among treatment-seeking adolescents in Southern California: participant characteristics and treatment response. J Subst Abus Treat 29:67–74
Reichel CM, Schwendt M, McGinty JF, Olive MF, See RE (2011) Loss of object recognition memory produced by extended access to methamphetamine self-administration is reversed by positive allosteric modulation of metabotropic glutamate receptor 5. Neuropsychopharmacology 36:782–792
Reichel CM, Ramsey LA, Schwendt M, Mcginty JF, See RE (2012) Methamphetamine-induced changes in the object recognition memory circuit. Neuropharmacology 62:1119–1126
Roberts DCS, Bennett SAL, Vickers GJ (1989) The estrous cycle affects cocaine self-administration on a progressive ratio schedule in rats. Psychopharmacology 98:408–411
Rogers J, Santis S, See R (2008) Extended methamphetamine self-administration enhances reinstatement of drug seeking and impairs novel object recognition in rats. Psychopharmacology 199:615–624
Roth ME, Carroll ME (2004) Sex differences in the acquisition of IV methamphetamine self-administration and subsequent maintenance under a progressive ratio schedule in rats. Psychopharmacology 172:443–449
Roth ME, Cosgrove KP, Carroll ME (2004) Sex differences in the vulnerability to drug abuse: a review of preclinical studies. Neurosci Biobehav Rev 28:533–546
Saucier DM, Shultz SR, Keller AJ, Cook CM, Binsted G (2008) Sex differences in object location memory and spatial navigation in Long–Evans rats. Anim Cogn 11:129–137
Schindler CW, Bross JG, Thorndike EB (2002) Gender differences in the behavioral effects of methamphetamine. Eur J Pharmacol 442:231–235
Schwendt M, Rocha A, See R, Pacchioni A, Mcginty J, Kalivas P (2009) Extended methamphetamine self-administration in rats results in a selective reduction of dopamine transporter levels in the prefrontal cortex and dorsal striatum not accompanied by marked monoaminergic depletion. J Pharmacol Exp Ther 331:555
Simpson J, Kelly JP (2012) An investigation of whether there are sex differences in certain behavioural and neurochemical parameters in the rat. Behav Brain Res 229:289–300
Vanderschuren LJMJ, Everitt BJ (2004) Drug seeking becomes compulsive after prolonged cocaine self-administration. Science 305:1017–1019
Warburton EC, Brown MW (2009) Findings from animals concerning when interactions between perirhinal cortex, hippocampus and medial prefrontal cortex are necessary for recognition memory. Neuropsychologia 48:2262–2272
Acknowledgments
This research was supported by NIDA grants DA016511 (RES), DA022658 (RES), HD055885 (CMR), Specialized Center on Research-Pilot Research Grant (CMR), and NIH grant C06 RR015455. The authors thank Meghin Gilstrap, Christina Johnson, and Melza van Roijen for technical assistance.
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Reichel, C.M., Chan, C.H., Ghee, S.M. et al. Sex differences in escalation of methamphetamine self-administration: cognitive and motivational consequences in rats. Psychopharmacology 223, 371–380 (2012). https://doi.org/10.1007/s00213-012-2727-8
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DOI: https://doi.org/10.1007/s00213-012-2727-8