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Sex differences in escalation of methamphetamine self-administration: cognitive and motivational consequences in rats

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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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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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Correspondence to Carmela M. Reichel.

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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

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