Role of D1/D2 dopamine receptors in the CA1 region of the rat hippocampus in the rewarding effects of morphine administered into the ventral tegmental area

Considerable evidences show that the VTA, as a major source of dopamine neurons projecting to cortical and limbic regions, has a major role in cognitive and motivating aspects of addiction. The current study assessed the ability of the selective D1 receptor antagonist SCH 23390 and D2 receptor antagonist sulpiride administrated into the CA1 region of hippocampus (dorsal hippocampus) to alter the rewarding effects of intra-VTA administration of morphine using the conditioned place preference (CPP). After bilaterally implantation of cannulae into the CA1 and/or VTA in adult male Wistar rats weighing 210–310 g, dose–response effects of different doses of intra-VTA morphine (0.03, 0.1, 0.3, 1 and 3 μg/side) on CPP paradigm were evaluated and animal displacement, conditioning score and locomotor activity were recorded by Ethovision software. In the next experiments, SCH 23390 (0.02, 0.05, 0.2 and 0.5 μg/side) or sulpiride (0.25, 0.75, 1.5 and 3 μg/side) were injected into the CA1, 5 min after intra-VTA injection of morphine during 3 days conditioning phase. Our results showed that intra-VTA morphine dose-dependently induces CPP in rats. Moreover, the blocking D1 and D2 receptors in the dorsal hippocampus decreased intra-VTA morphine-induced CPP significantly (P < 0.01). Intra-CA1 administration of these antagonists alone, in all doses, could not induce CPP. We suggest that D1 and D2 receptors in the CA1 region of hippocampus have a key role in the development of CPP induced by morphine at the level of the VTA. It seems that there is an interaction between dopaminergic and opioidergic systems in these areas in reward circuit.

► Intra-VTA morphine dose-dependently induces conditioned place preference in rats.
► Blocking D1 receptors in the CA1 decreases intra-VTA morphine-induced CPP.
► D2 receptor antagonist (sulpiride) in CA1 decreases intra-VTA morphine-induced CPP.
► Intra-CA1 administration of D1/D2 receptor antagonists alone could not induce CPP.