δ-Opioid Receptor Expression in the Ventral Tegmental Area Protects Against Elevated Alcohol Consumption

• DOI: 10.1523/jneurosci.4569-08.2008
• Publication Date: 2008-11-26T18:29:23Z
• Authors: Elyssa B. Margolis; Howard L. Fields; Gregory O. Hjelmstad; Jennifer M. Mitchell
• Keywords: DAMGO; μ-opioid receptor; Brain stimulation reward

Alcoholism is a complex and debilitating syndrome affecting ∼140 million people worldwide. However, not everyone who consumes ethanol develops abuse, raising the possibility that some individuals have protective mechanism inhibits elevated alcohol consumption. We tested hypothesis δ-opioid receptor (DOR) plays such role. Here we show DOR activity in ventral tegmental area (VTA) robustly decreases consumption rats these effects depend on baseline Intra-VTA microinjection of agonist DPDPE drinking, particularly low-drinking animals. Furthermore, VTA selective antagonist TIPP-Ψ increases drinking low, but high, drinkers this increase blocked by comicroinjection GABA A bicuculline. Using electrophysiological techniques found brain slices from presynaptically mediated IPSCs low drinkers, high or naive animals, most likely through activation DORs terminals. This DOR-mediated inhibition also correlates inversely with behavioral anxiety measured plus maze. In contrast, presynaptic μ- opioid DAMGO significantly reduced both high- (<30%) compared age-matched nondrinking controls (>70%). Together, our findings demonstrate nature identify an important new target for therapeutic intervention alcoholism.