Morphine-induced place preference: Involvement of the central amygdala NMDA receptors

In the present study, the effects of bilateral injections of N-methyl-d-aspartate (NMDA) receptor agonist and/or antagonist into the central amygdala (CeA) on the acquisition and expression of morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats. Animals that received 3 daily subcutaneous (s.c.) injections of morphine (1–9 mg/kg) or saline (1.0 ml/kg) indicated a significant preference for compartment paired with morphine in a dose dependent manner. Intra-CeA administration of the NMDA (0.01, 0.1 or 1 μg/rat) with an ineffective dose of morphine (1 mg/kg, s.c.) elicited a significant CPP. Administration of the non-competitive NMDA receptor antagonist, MK-801 (0.1, 0.3 or 0.5 μg/rat), into the central amygdala dose-dependently inhibited the morphine (6 mg/kg, s.c.)-induced place preference. Furthermore, intra-CeA administration of MK-801 (0.25, 0.5 or 1 μg/rat) reduced the response induced by NMDA (1 μg/rat, intra-CeA) plus morphine (1 mg/kg, s.c.). Neither NMDA nor MK-801 alone produce a significant place preference or place aversion. Moreover, intra-CeA injection of NMDA but not MK-801 before testing significantly increased the expression of morphine (6 mg/kg, s.c.)-induced place preference. NMDA or MK-801 injections into the CeA had no effects on locomotor activity on the testing sessions. These results suggest that the NMDA receptor mechanisms in the central amygdala may be involved in the acquisition and expression of morphine-induced place preference.