Oxytocin directly administered into the nucleus accumbens core or subthalamic nucleus attenuates methamphetamine-induced conditioned place preference

Accumulating evidence indicates that the neuropeptide oxytocin (OXY) may modulate reward-related behavioural responses to methamphetamine (METH) administration. Limited research has examined the effect of OXY on METH-induced conditioned place preference (CPP) and little is known about the neural mechanisms involved. A Fos immunohistochemistry study recently demonstrated that peripheral OXY administration reduced METH-induced Fos expression within the nucleus accumbens (NAc) core and subthalamic nucleus (STh) in rats. The current study aimed to (i) investigate the effect of systemically administered OXY on METH-induced CPP, (ii) determine the effectiveness of a single-trial CPP procedure with METH, in order to (iii) evaluate whether pretreatment with OXY injected directly into the NAc core or the STh attenuates METH-induced CPP. Results showed that male Sprague Dawley rats learned to associate unique compartmental cues with METH (1 mg/kg, i.p.) such that they spent more time in the METH-paired compartment and less time in the saline-paired compartment. Pretreatment with systemic OXY (0.6 mg, i.p.), or OXY (0.6 ng, i.c.) microinjected into the NAc core or the STh prior to METH administration attenuated the formation of a CPP to METH. This provides further evidence that OXY acts within either the NAc core or the STh to reduce the rewarding effects of METH administration.

► A conditioned place preference for methamphetamine formed after a single pairing.
► A preference did not form after an oxytocin pretreatment in the accumbens core.
► A preference did not form after an oxytocin pretreatment in the subthalamic nucleus.
► Methamphetamine hyperactivity was not reduced by a local oxytocin injection.