Development of rapid tolerance to ethanol-stimulated serotonin release in the ventral hippocampus.
This study was designed to examine the effects of acute intraperitoneal (i.p.) ethanol injection on the extracellular levels of serotonin (5-HT) in the ventral hippocampus (vHIP) and to determine whether a single prior exposure to ethanol could alter the response to a second dose of ethanol given 24 hr later. In the first experiment, in vivo microdialysis coupled with high pressure liquid chromatography-electrochemical detection (HPLC-EC) was used to assess the effects of 1.0, 1.75, and 2.5 g/kg ethanol on vHIP 5-HT extracellular levels in ethanol-naïve adult male Wistar rats. The largest dose significantly increased the extracellular concentration of 5-HT (p < 0.001) to a maximum of approximately 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 transiently increased 5-HT levels above baseline; however, no significant increase was observed with 1.0 g/kg ethanol. The results of the second experiment demonstrated that the i.p. dose of 2.5 g/kg ethanol had no significant effect on the extracellular levels of 5-HT if rats had been given a single i.p. 2.5 g/kg dose of ethanol 24 hr earlier. Because the vHIP receives a major 5HT input from the median raphe nucleus (MRN), the results suggest that acute ethanol activates the MRN 5-HT system projecting to the vHIP and that rapid tolerance develops to the activating effects of alcohol on this pathway.
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis 46202-4887, USA.
D J
DJ
Bare
J H
JH
McKinzie
W J
WJ
McBride
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D000431:Ethanol / Q000493:pharmacokinetics / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D008297:Male; D017551:Microdialysis; D011903:Raphe Nuclei / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D013268:Stimulation, Chemical
D012701:Serotonin; D000431:Ethanol