Dopamine-2 receptors in the arcuate nucleus modulate cocaine-seeking behavior

Beta-endorphin is an endogenous opioid peptide, implicated in the behavioral effects of drugs of abuse. It is synthesized in the arcuate nucleus and secreted into the nucleus accumbens. In the present study, we examined the interaction between arcuate nucleus dopaminergic cells and accumbal beta-endorphin, during cocaine exposure. Using microdialysis, we found that blockade of arcuate dopamine-2 receptors with a selective antagonist significantly attenuated cocaine-induced increases of beta-endorphin levels in the nucleus accumbens. Moreover, rats chronically exposed to cocaine using the self-administration paradigm displayed extinction-like behavior following blockade of dopamine-2 receptors. These findings indicate that dopaminergic neurons in the arcuate nucleus may induce the secretion of beta-endorphin in the nucleus accumbens, and that they are implicated in the cocaine reward pathway.