title: Systemically administered oxytocin decreases methamphetamine activation of the subthalamic nucleus and accumbens core and stimulates oxytocinergic neurons in the hypothalamus.
abstract: Recent preclinical evidence indicates that the neuropeptide oxytocin may have potential in the treatment of drug dependence and drug withdrawal. Oxytocin reduces methamphetamine self-administration, conditioned place preference and hyperactivity in rodents. However, it is unclear how oxytocin acts in the brain to produce such effects. The present study examined how patterns of neural activation produced by methamphetamine were modified by co-administered oxytocin. Male Sprague-Dawley rats were pretreated with either 2 mg/kg oxytocin (IP) or saline and then injected with either 2 mg/kg methamphetamine (IP) or saline. After injection, locomotor activity was measured for 80 minutes prior to perfusion. As in previous studies, co-administered oxytocin significantly reduced methamphetamine-induced behaviors. Strikingly, oxytocin significantly reduced methamphetamine-induced Fos expression in two regions of the basal ganglia: the subthalamic nucleus and the nucleus accumbens core. The subthalamic nucleus is of particular interest given emerging evidence for this structure in compulsive, addiction-relevant behaviors. When administered alone, oxytocin increased Fos expression in several regions, most notably in the oxytocin-synthesizing neurons of the supraoptic nucleus and paraventricular nucleus of the hypothalamus. This provides new evidence for central actions of peripheral oxytocin and suggests a self-stimulation effect of exogenous oxytocin on its own hypothalamic circuitry. Overall, these results give further insight into the way in which oxytocin might moderate compulsive behaviors and demonstrate the capacity of peripherally administered oxytocin to induce widespread central effects.
authors: Brain & Mind Research Institute, University of Sydney, NSW, Australia.
authors: Dean S
authors: DS
authors: Carson
authors: Glenn E
authors: GE
authors: Hunt
authors: Adam J
authors: AJ
authors: Guastella
authors: Lachlan
authors: L
authors: Barber
authors: Jennifer L
authors: JL
authors: Cornish
authors: Jonathon C
authors: JC
authors: Arnold
authors: Aurelie A
authors: AA
authors: Boucher
authors: Iain S
authors: IS
authors: McGregor
mesh_terms: D019969:Amphetamine-Related Disorders / Q000503:physiopathology*; D000818:Animals; D003192:Compulsive Behavior / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007031:Hypothalamus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000187:drug effects / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000503:physiopathology; D010121:Oxytocin / Q000378:metabolism / Q000494:pharmacology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000503:physiopathology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D020531:Subthalamic Nucleus / Q000187:drug effects* / Q000503:physiopathology; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000503:physiopathology
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D008694:Methamphetamine; D010121:Oxytocin; D004298:Dopamine