Alpha-1 Adrenergic Receptor Agonism in the Lateral Hypothalamus may Blunt Voluntary Binge-like Ethanol Consumption in Mice

Undergraduates: Corryn Chaimowitz, Nathan Burnham

Faculty Advisor: Todd Thiele
Department: Psychology & Neuroscience

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The role of the lateral hypothalamus (LH) in reward and feeding behavior has been extensively examined in relation to its role in binge-like ethanol consumption. Studies suggest a linkage between norepinephrine and binge drinking behavior originating from the locus coeruleus (LC) and A2 region of the nucleus tractus solitaries (NTS). These two areas are known to play a role in both reward-seeking and consummatory behavior. Recent (unpublished) data shows a projection from these regions to the LH, suggesting that noradrenergic innervation of the LH may influence consummatory behavior including ethanol consumption. To assess this possibility, we chose to pharmacologically activate alpha-1 adrenergic receptors in the LH. Male and female C57BL/6J mice were stereotaxically implanted with LH-targeted cannulae. Mice were then run in consecutive 4-day ¿¿¿Drinking-in-the-Dark¿¿¿ (DID) cycles in Latin square fashion. Our manipulation revealed that alpha-1 agonism in the LH dose-and time-dependently reduces ethanol consumption but had no effect on sucrose consumption. The highest dose tested failed to alter locomotor activity in an open field test, but appears to be anxiogenic as measured by time spent in the center portion of the chamber. These findings suggest that alpha-1 adrenergic receptor activity may modulate binge-like ethanol consumption uniquely. Ongoing studies seek to elucidate the relative influence of A2¿¿¿LH and LC¿¿¿LH pathways in modulation of this effect via DREADD technology.