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.
Bare
D J
DJ
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis 46202-4887, USA.
McKinzie
J H
JH
McBride
W J
WJ
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