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The interaction of oxytocin and vasopressin systems in reducing relapse to methamphetamine abuse
thesisposted on 2022-03-28, 13:28 authored by Nicholas Adams Everett
Methamphetamine (METH) is a highly addictive psychostimulant. Currently there are no approved pharmacotherapies for METH dependence, although animal models of drug use have highlighted the therapeutic potential of the neuropeptide oxytocin (OXY) in treating METH dependence. The nucleus accumbens (NAc) core, an important brain region for addiction and relapse, has been identified as an important site for OXY-METH interactions. However, the inhibitory effect of OXY administration on relapse to METH-seeking behaviour does not appear to be mediated by the oxytocin receptor (OTR) within the NAc core, and further it has not yet been shown if the effect of systemic administration of OXY to reduce METH-seeking behaviour is mediated by the OTR. Due to the increasing evidence of OXY interactions with the vasopressin V1a receptor, the present thesis investigated a role for this receptor in mediating the attenuating effect of exogenous OXY on METH-related behaviours. The intravenous drug self-administration model of reinstatement was utilised to explore this interaction following systemic administration, and locally within the NAc core. This study is the first to demonstrate that the V1a receptor, but not the OTR, plays an important role in mediating the effects of systemic administration of OXY to attenuate METH-primed reinstatement of drug-seeking and acute METH-hyperactivity. The involvement of the V1a receptor in these inhibitory effects of OXY within the NAc core on METH-seeking behaviours remains undetermined. Results are discussed in light of other neural substrates potentially involved in OXY-METH interactions, and the advancement of OXY-based pharmacotherapies for METH-dependence.