Effect of systemically administered oxytocin on dose response for methylphenidate self-administration and mesolimbic dopamine levels.

Abstract

The neuropeptide oxytocin (OT) alters behaviors related to the administration of drugs of abuse, including stimulants. OT also plays a key role in social bonding, which involves an interaction between OT and dopamine (DA) in the nucleus accumbens (NAc). The nature of the interaction between OT and DA in the striatum in the context of psychostimulants is unclear. We investigated the effect of OT, delivered intraperitoneally, on the methylphenidate (MP) dose-response function for self-administration in rats. Food was used as a control condition. In a microdialysis study, we measured the effect of intraperitoneal OT on MP-stimulated striatal DA levels. Systemic OT pretreatment caused a downward shift in the MP dose-response function for self-administration, while having no effect on motor activity. OT also caused a reduction in food self-administration, although a significantly higher dose of OT was required for this effect compared with that required for a reduction of MP self-administration. Systemic OT pretreatment caused a potentiation of MP-stimulated DA levels in the NAc shell but not in the core. The significance of these findings is discussed, including the potential of OT as a therapeutic agent for addictive disorders.