DEVELOPMENT OF RAPID TOLERANCE TO ETHANOL-STIMULATED SEROTONIN RELEASE IN THE VENTRAL HIPPOCAMPUS

This study was designed to examine the effects of acute intraperitonea l tip) ethanol injection on the extracellular levels of serotonin (5-H T) in the ventral hippocampus (vHIP) and to determine whether a single prior exposure to ethanol could alter the response to a second dose o f ethanol given 24 hr later. In the first experiment, in vivo microdia lysis coupled with high pressure liquid chromatography-electrochemical detection (HPLC-EC) was used to assess the effects of 1.0, 1.75, and 25 g/kg ethanol on vHIP 5-HT extracellular levels in ethanol-naive adu lt male Wistar rats. The largest dose significantly increased the extr acellular concentration of 5-HT (p < 0.001) to a maximum of approximat ely 180% of baseline values within 50 min; thereafter, the levels of 5 -HT began to return toward baseline. The 1.75 g/kg dose also transient ly increased 5-HT levels above baseline; however, no significant incre ase was observed with 1.0 g/kg ethanol, The results of the second expe riment demonstrated that the ip dose of 2.5 g/kg ethanol had no signif icant effect on the extracellular levels of 5-HT if rats had been give n a single ip 2.5 g/kg dose of ethanol 24 hr earlier. Because the vHIP receives a major 5-HT input from the median raphe nucleus (MRN), the results suggest that acute ethanol activates the MRN 5-HT system proje cting to the vHIP and that rapid tolerance develops to the activating effects of alcohol on this pathway.