In the present study, the effects of bilateral intra-hippocampal CA1 (intra-CA1) injections of GABA(A) receptor agonist and/or antagonist on the acquisition and expression of morphine-induced place preference in mate Wistar rats have been investigated. The conditioning treatments with subcutaneous (s.c.) injections of different doses of morphine (0.5-7.5 mg/kg) induced a conditioned place preference (CPP) for the drug-associated place in a dose-dependent manner. Intra-CA1 administration of the GABA(A) receptor agonist, muscinnot (0.25, 0.5 and 1 mu g/ rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP. Intra-CA1 injections of different doses of the GABAA receptor antagonist, bicucultine (0.25, 0.5 and 1 mu g/rat), in combination with an ineffective dose of morphine (0.5 mg/kg, s.c.) elicited a significant CPP However, muscimol or bicuculline by themselves did not elicit any effect on place conditioning. Furthermore, the muscimol-induced inhibition of morphine response was reversed by bicucultine (1 mu g/rat, intra-CA1) administration. On the other hand, the bilateral intra-CA1 injections of muscimot (0.25, 0.5 and 1 mu g/rat) or bicuculline (0.5, 1 and 2 mu g/rat) significantly decreased the expression of morphine-induced CPP. Intra-CA1 administration of different doses of muscimot or bicuculline had no effect on locomotor activity in the testing phase. Our data indicated that the GABAA receptors of the hippocampal CA1 regions may play an important role in the acquisition and expression of morphine-induced place preference. (c) 2006 Elsevier B.V. and ECNP. All rights reserved.