GABA A receptors of hippocampal CA1 regions are involved in the acquisition and expression of morphine-induced place preference Ameneh Rezayof a , Samira Razavi a , Ali Haeri-Rohani a , Yassaman Rassouli a , Mohammad-Reza Zarrindast b,c,d, * a School of Biology, University College of Science, University of Tehran, Tehran, Iran b Department of Pharmacology and Iranian National Center for Addiction Studies, Tehran University of Medical Sciences, Tehran, Iran c School of Cognitive Science, Institute for Studies in Theoretical Physics and Mathematics, Tehran, Iran d Institute for Cognitive Science Studies, Tehran, Iran Received 9 July 2005; received in revised form 29 January 2006; accepted 14 February 2006 Abstract 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 male 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, muscimol (0.25, 0.5 and 1 Ag/ rat) significantly inhibited the morphine (5 mg/kg, s.c.)-induced CPP. Intra-CA1 injections of different doses of the GABA A receptor antagonist, bicuculline (0.25, 0.5 and 1 Ag/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 bicuculline (1 Ag/rat, intra-CA1) administration. On the other hand, the bilateral intra-CA1 injections of muscimol (0.25, 0.5 and 1 Ag/rat) or bicuculline (0.5, 1 and 2 Ag/rat) significantly decreased the expression of morphine-induced CPP. Intra-CA1 administration of different doses of muscimol or bicuculline had no effect on locomotor activity in the testing phase. Our data indicated that the GABA A receptors of the hippocampal CA1 regions may play an important role in the acquisition and expression of morphine-induced place preference. D 2006 Elsevier B.V. and ECNP. All rights reserved. 0924-977X/$ - see front matter D 2006 Elsevier B.V. and ECNP. All rights reserved. doi:10.1016/j.euroneuro.2006.02.003 * Corresponding author. Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences, P. O. Box 13145-784, Tehran, Iran. Tel.: +98 21 6112801; fax: +98 21 640 2569. E-mail address: zarinmr@ams.ac.ir (M.-R. Zarrindast). KEYWORDS Morphine; Conditioned place preference; GABA A receptor agents; Dorsal hippocampus; Rat European Neuropsychopharmacology (2007) 17, 24—31 www.elsevier.com/locate/euroneuro