title: Sex differences in methamphetamine seeking in rats: impact of oxytocin.
abstract: Previous evidence in an animal model of drug self-administration and drug seeking showed that acute oxytocin decreased methamphetamine (meth) seeking in male rats, suggesting potential clinical efficacy for the treatment of psychostimulant addiction. However, based on the well-established role of oxytocin in reproduction and pair bond formation, it is important to know how this effect extrapolates to females. Here, we tested whether oxytocin (1mg/kg, IP) would decrease meth seeking in female rats across various stages of the estrous cycle (Experiment 1). Freely cycling Long Evans female rats self-administered meth (IV) in 2-h daily sessions, followed by daily extinction sessions. Following extinction, rats received oxytocin (0, 0.3, or 1mg/kg, IP) 30min before a meth priming injection (1mg/kg, IP) to assess reinstatement of meth seeking. Next, we examined the effects of oxytocin on motivated meth- and sucrose-taking and seeking in male and female rats. In separate experiments, males and females self-administered meth (Experiment 2) or sucrose (Experiment 3) until responding was stabilized along a fixed ratio (FR) 5 schedule of reinforcement. Subsequently, rats received either oxytocin or vehicle prior to self-administration along a progressive ratio (PR) schedule of reinforcement. Rats were subsequently tested for cue-, meth-, and stress-induced reinstatement after pretreatment with oxytocin or vehicle. While oxytocin reduced meth seeking in females, we found that estrous cycle stage (as determined from vaginal cytology) did not influence meth-primed reinstatement or the ability of oxytocin to decrease reinstatement of meth seeking. Oxytocin reduced PR responding for meth only in females. Females responded more than males during cue-induced reinstatement of meth and sucrose seeking, and oxytocin reduced this responding only in meth females. In both sexes, oxytocin attenuated meth seeking in response to a meth prime and yohimbine (a pharmacological stressor). The results suggest that oxytocin may have efficacy as a treatment of meth addiction in both sexes; however, females may show greater response to oxytocin treatment for the prevention of relapse.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Brittney M
authors.initials: BM
authors.lastname: Cox
authors.forename: Amy B
authors.initials: AB
authors.lastname: Young
authors.forename: Ronald E
authors.initials: RE
authors.lastname: See
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Reichel
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D058999:Drug-Seeking Behavior / Q000187:drug effects; D030762:Estrous Cycle / Q000187:drug effects / Q000502:physiology; D005260:Female; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012054:Reinforcement, Psychology; D012646:Self Administration; D012727:Sex Characteristics
chemical_list: D000697:Central Nervous System Stimulants; D008694:Methamphetamine; D010121:Oxytocin
keywords: Methamphetamine; Oxytocin; Progressive ratio; Reinstatement; Self-administration; Sex differences