title: Reinstatement of methamphetamine seeking in male and female rats treated with modafinil and allopregnanolone.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Psychiatry, University of Minnesota, Minneapolis, MN 55455, USA. holt0324@umn.edu
authors.forename: Nathan A
authors.initials: NA
authors.lastname: Holtz
authors.forename: Anthony
authors.initials: A
authors.lastname: Lozama
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Prisinzano
authors.forename: Marilyn E
authors.initials: ME
authors.lastname: Carroll
mesh_terms: D019969:Amphetamine-Related Disorders / Q000188:drug therapy* / Q000523:psychology; D000818:Animals; D001559:Benzhydryl Compounds / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D005260:Female; D008297:Male; D008694:Methamphetamine; D000077408:Modafinil; D011280:Pregnanolone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012737:Sex Factors
chemical_list: D001559:Benzhydryl Compounds; D002492:Central Nervous System Depressants; D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D011280:Pregnanolone; D000077408:Modafinil