Effects of oxytocin on methamphetamine-induced conditioned place preference and the possible role of glutamatergic neurotransmission in the medial prefrontal cortex of mice in reinstatement.

Jia Qi^a, Jing-Yu Yang^a, Fang Wang^a, Ya-Nan Zhao^a, Ming Song^b and Chun-Fu Wu^a,*,

^aDepartment of Pharmacology, Life Science and Biopharmaceutics School, Shenyang Pharmaceutical University, Shenyang 110016, China

^bLiaoning Institute of Crime Detectives, Shenyang 110032, China

Aim: To investigate the effects of oxytocin (OT), a neurohypophyseal neuropeptide, on the conditioned place preference (CPP) induced by methamphetamine (MAP) in mice and the possible role of glutamatergic neurotransmission in the reinstatement of CPP. Methods: CPP model was established by MAP administration (2.0 mg/kg, i.p.). Extracellular glutamate (Glu) levels in the medial prefrontal cortex (mPFC) were determined using microdialysis coupled to a high-performance liquid chromatography (HPLC) with a fluorescence detection system. Results: The results showed that OT (0.1, 0.5, 2.5 μg, i.c.v.) significantly inhibited the acquisition and facilitated the extinction of MAP-induced CPP and abolished the reinstatement of CPP induced by restraint stress. This effect of OT could be attenuated by atosiban (Ato, 2.0 μg, i.c.v.), a selective OT-receptor antagonist. OT failed to block the expression and the reinstatement of CPP induced by MAP challenge. Furthermore, OT markedly inhibited Glu levels induced by restraint stress in CPP mice, but not those induced by MAP priming. Ato also attenuated the effects of OT on the changes in Glu levels. Conclusion: These findings suggest that OT inhibits drug reward-related behaviors induced by MAP via the OT receptor, and OT blocks the reinstatement of CPP, at least partially, by interfering with the glutamatergic system in the mPFC.

Keywords: Methamphetamine; Oxytocin; Conditioned place preference; Microdialysis; Glutamate; Medial prefrontal cortex

* Corresponding author, chunfuw@gmail.com

1两岸三地药理学学术会议(第一轮通知).doc