Dorsal hippocampal muscarinic and nicotinic receptors are involved in mediating morphine reward.

In the present study, the effects of bilateral injections of cholinergic agents into the hippocampal CA1 region on morphine-induced conditioned place preference (CPP) were investigated in male Wistar rats. Subcutaneous (s.c.) administration of different doses of morphine sulphate (0.5-6 mg/kg) produced a dose-dependent CPP. Using a 3-day schedule of conditioning, it was found that intra-CA1 administration of the anticholinesterase, physostigmine (2, 4 and 8 microg/rat) significantly potentiated the morphine (0.5 mg/kg)-induced CPP. Moreover, intra-CA1 administration of the muscarinic receptor antagonist, atropine (1, 4 and 7 microg/rat) inhibited the morphine (6 mg/kg)-induced CPP dose-dependently. On the other hand, atropine (7 microg/rat, intra-CA1) reversed the physostigmine-induced potentiation of the morphine response. Furthermore, intra-CA1 administration of nicotine (0.5, 0.75 and 1 microg/rat) with an ineffective dose of morphine (0.5 mg/kg) elicited a significant CPP. Bilateral injections of different doses of the nicotinic receptor antagonist, mecamylamine (2, 4 and 8 microg/rat) into the CA1 regions significantly inhibited the morphine (6 mg/kg)-induced CPP. Moreover mecamylamine (8 microg/rat, intra-CA1) decreased the effect of nicotine-induced potentiation of the morphine response. Intra-CA1 injections of physostigmine, atropine, nicotine or mecamylamine alone did not induce a significant place preference or place aversion. It may be concluded that the muscarinic and nicotinic receptors of the hippocampal CA1 regions play an important role in morphine reward.