Title: Effects of Chronic Ethanol Exposure and Withdrawal on Dendritic Morphology in the Nucleus Accumbens

Authors: Veronica L. Peterson1, J. P. Rice1, B. A. McCool2, and D. A. Hamilton1

Affiliations: 1Department of Psychology and Neurosciences, University of New Mexico, 2Department of Physiology and Pharmacology, Wake Forrest University

Abstract: The nucleus accumbens (NAc) is critical for reward learning and reinforcement. Being a major terminus of the mesolimbic dopaminergic pathway, examination of the NAc provides information to help understand the role of this pathway in addiction and drug seeking behaviors. Negative reinforcement related to withdrawal avoidance may also be a function of the NAc. Prior work from our laboratory demonstrated that prenatal ethanol exposure reduced dendritic length and branching in medium spiny neurons (MSNs) of the NAc shell but not the core, which may partially explain increased drug administration observed following prenatal exposure. The present study was designed to examine the effects of short (24 hour) and long (7 day) term withdrawal from chronic ethanol exposure on dendritic morphology in the NAc in adulthood. Adult male Sprague Dawley rats were placed in airtight Plexiglas chambers and received 10 consecutive days of ethanol vapor (~37mg/L air) during the light-cycle (12hr/day). This exposure produces blood-ethanol concentrations in the range of 150-200mg/dL. Ethanol exposed animals were then euthanized either 24 hours or seven days after the last ethanol exposure. Control animals were housed under identical conditions but received only room air during the 10-day exposure period. Golgi-Cox stained MSNs from the NAc core and shell were traced at 500X magnification using the camera lucida technique. Dendritic length and branching were quantified by counting ring intersections (Sholl analysis) and branch points on 10 neurons per animal (5/hemisphere) in each region of interest. In the nucleus accumbens shell, neither dendritic branching nor dendritic length were altered in any of the treatment groups. In the nucleus accumbens core however, both dendritic branching and length were significantly increased in the 7-day withdrawal group relative to both the 24-hour withdrawal and control groups. These data suggest that withdrawal from chronic ethanol produces dramatic increases in MSN dendritic branching and length in the nucleus accumbens core but not in the shell. These time-dependent increases were manifest only after prolonged withdrawal suggesting they reflect a long-term, plastic process initiated by chronic ethanol exposure.

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