Hippocampal Contributions to Dopamine Receptor-Mediated Effects of Cocaine

Several areas of the hippocampal formation receive dopaminergic innervation from the ventral tegmental area and substantia nigra pars compacta and thus contain synapses where cocaine can exert its pharmacological effects. Here, we review recent findings indicating that cocaine exposure elicits increases in dopamine neurotransmission within the hippocampal formation and produces prolonged hippocampal neuroplasticity, at least in part via D1-like dopamine receptor-dependent mechanisms. In turn, cocaine-induced hippocampal neuroplasticity augments dopamine release and D1-like receptor stimulation in brain regions where hippocampal and dopaminergic axons coterminate and alters dopamine neuronal activity via feedback to the midbrain. The septal and temporal subdivisions of the hippocampal formation differ in dopaminergic innervation and extrahippocampal connectivity and play complementary roles in phenomena related to cocaine addiction. Specifically, D1-like receptor stimulation in the septal hippocampal formation controls cocaine-associated contextual learning and memory, while the temporal hippocampal formation modulates dopamine neurotransmission to encode cocaine reward and reinforcement as well as the motivational effects of cocaine-associated environmental stimuli.