title: Oxytocin via its receptor affects restraint stress-induced methamphetamine CPP reinstatement in mice: Involvement of the medial prefrontal cortex and dorsal hippocampus glutamatergic system.
abstract: Our previous study revealed that intracerebroventricular oxytocin (OT) markedly inhibited the restraint stress-priming conditioned place preference (CPP) reinstatement induced by methamphetamine (MAP) via the glutamatergic system. In this study, the effect of microinjection with OT into mesocorticolimbic regions, the medial prefrontal cortex (mPFC) and the dorsal hippocampus (DHC), on the restraint stress-priming CPP reinstatement were further studied. The results showed that a 15-min restraint stress significantly reinstated MAP-induced CPP, which was inhibited by the microinjection of OT (0.5 and 2.5μg/μl/mouse) into the mPFC. Atosiban (Ato), a selective inhibitor of OT receptor, could absolutely block the effect of OT (2.5μg/μl/mouse). The reinstatement was inhibited by microinjecting with OT (2.5 but not 0.5μg/μl/mouse) into the DHC, which could not be reversed by Ato. Western blotting results showed that the levels of GLT1, VGLUT2, NR2B, p-ERK1/2 and p-CREB expressions in the mPFC were increased and CaMKII was decreased markedly after the stress-priming MAP-induced CPP reinstatement test. OT blocked the changing levels of GLT1, VGLUT2, NR2B, p-CREB and CaMK II, which were reversed by Ato, but failed to affect the elevated expression of p-ERK1/2. In DHC, the levels of VGLUT2, p-ERK1/2 and CREB expressions were reduced during the stress-induced reinstatement, which could be reversed by OT and further abolished by Ato. The present results suggest that mPFC and DHC play differential roles in restraint stress-priming CPP reinstatement induced by MAP and OT via OT receptor affects the reinstatement in which the glutamatergic system is involved.
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China. Electronic address: whan1@uthsc.edu.
authors.forename: Wen-Yan
authors.initials: WY
authors.lastname: Han
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Ping
authors.initials: P
authors.lastname: Du
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Shi-Yuan
authors.initials: SY
authors.lastname: Fu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: Liaoning Institute of Crime Detectives, 110032 Shenyang, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Song
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China. Electronic address: wucf@syphu.edu.cn.
authors.forename: Chun-Fu
authors.initials: CF
authors.lastname: Wu
authors.affiliation: Department of Pharmacology, Shenyang Pharmaceutical University, 110016 Shenyang, PR China. Electronic address: yangjingyu2006@gmail.com.
authors.forename: Jing-Yu
authors.initials: JY
authors.lastname: Yang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D018698:Glutamic Acid / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D007103:Immobilization; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D051379:Mice; D010121:Oxytocin / Q000502:physiology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000502:physiology*; D013312:Stress, Physiological
chemical_list: D018045:Receptors, Oxytocin; D018698:Glutamic Acid; D008694:Methamphetamine; D010121:Oxytocin
keywords: Dorsal hippocampus; Medial prefrontal cortex; Methamphetamine; Oxytocin; Reinstatement; Restraint stress