Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone

Nathan A. Holtz, Anthony Lozama, Thomas E. Prisinzano, Marilyn E. Carroll

Research output: Contribution to journalArticlepeer-review

47 Scopus citations


Background: Sex differences in methamphetamine (METH) use (females > males) have been demonstrated in clinical and preclinical studies. This experiment investigated the effect of sex on the reinstatement of METH-seeking behavior in rats and determined whether pharmacological interventions for METH-seeking vary by sex. Treatment drugs were modafinil (MOD), an analeptic, and allopregnanolone (ALLO), a neuroactive steroid and progesterone metabolite. Method: Male and female rats were trained to self-administer i.v. infusions of METH (0.05. mg/kg/infusion). Next, rats self-administered METH for a 10-day maintenance period. METH was then replaced with saline, and rats extinguished lever-pressing behavior over 18 days. A multi-component reinstatement procedure followed whereby priming injections of METH (1. mg/kg) were administered at the start of each daily session, preceded 30. min by MOD (128. mg/kg, i.p.), ALLO (15. mg/kg, s.c.), or vehicle treatment. MOD was also administered at the onset of the session to determine if it would induce the reinstatement of METH-seeking behavior. Results: Female rats had greater METH-induced reinstatement responding compared to male rats following control treatment injections. MOD (compared to the DMSO control) attenuated METH-seeking behavior in male and female rats; however, ALLO only reduced METH-primed responding in females. MOD alone did not induce the reinstatement of METH-seeking behavior. Conclusions: These results support previous findings that females are more susceptible to stimulant abuse compared to males, and ALLO effectively reduced METH-primed reinstatement in females. Further, results illustrate the utility of MOD as a potential agent for prevention of relapse to METH use in both males and females.

Original languageEnglish
Pages (from-to)233-237
Number of pages5
JournalDrug and Alcohol Dependence
Issue number1-3
StatePublished - Jan 1 2012

Bibliographical note

Funding Information:
This research was supported by the National Institute on Drug Abuse (NIDA) grants R01 DA018151S1 (TEP), R01 DA003240, K05 DA015267 (MEC). NIDA had no additional part in the study design; in data collection, analysis, or interpretation; in writing; nor in the decision to submit this manuscript for publication.


  • Allopregnanolone
  • Methamphetamine
  • Modafinil
  • Rats
  • Reinstatement
  • Sex differences

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)


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