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

Drug Alcohol Depend. 2012 Jan 1;120(1-3):233-7. doi: 10.1016/j.drugalcdep.2011.07.010. Epub 2011 Aug 5.


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 (1mg/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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amphetamine-Related Disorders / drug therapy*
  • Amphetamine-Related Disorders / psychology
  • Animals
  • Benzhydryl Compounds / pharmacology*
  • Central Nervous System Depressants / pharmacology*
  • Central Nervous System Stimulants / pharmacology*
  • Female
  • Male
  • Methamphetamine*
  • Modafinil
  • Pregnanolone / pharmacology*
  • Rats
  • Rats, Wistar
  • Sex Factors


  • Benzhydryl Compounds
  • Central Nervous System Depressants
  • Central Nervous System Stimulants
  • Methamphetamine
  • Pregnanolone
  • Modafinil