Ethanol-stimulated serotonin release in the ventral hippocampus: an absence of rapid tolerance for the alcohol-preferring P rat and insensitivity in the alcohol-nonpreferring NP rat.
This study examined the acute effects of intraperitoneal administration of ethanol on the extracellular levels of serotonin (5-HT) in the ventral hippocampus (vHIP) of adult, male alcohol-preferring P and -nonpreferring NP rats. Using in vivo microdialysis coupled with HPLC and electrochemical detection, the effects of acute administration of saline or 1.0, 1.75, or 2.5 g/kg ethanol on the extracellular levels of 5-HT in the vHIP were examined. Saline and 1.0 g/kg ethanol did not alter the extracellular levels of 5-HT. However, the 1.75-g/kg dose resulted in a transient increase in 5-HT levels in the vHIP of P rats only. Administration of 2.5 g/kg ethanol increased 5-HT levels to 180% of baseline in P rats (P<.05), but was without effect on NP rats. The 2.5-g/kg dose also significantly increased the extracellular levels of 5-HT in the vHIP of P rats, which had been pretreated with the same dose of ethanol 18-24 h earlier (P<.05). Comparison of the response of ethanol pretreated P rats with animals that had been pretreated with saline 24 h earlier did not reveal any significant differences in ethanol-stimulated increases in 5-HT levels between the groups. These data suggest that ethanol may activate terminals of the median raphe 5-HT system in P rats because the vHIP receives its 5-HT inputs primarily from the median raphe nucleus (MRN). Rapid tolerance does not develop to this activation of the system in the vHIP of P rats. In addition, the data suggest that the 5-HT system in the vHIP of NP rats may be relatively insensitive to the stimulating effect of acute ethanol of 5-HT release.
Thielen
R J
RJ
Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indianapolis, IN 46202, USA. rthielen@iupui.edu
Bare
D J
DJ
McBride
W J
WJ
Lumeng
L
L
Li
T-K
TK
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013045:Species Specificity
D002492:Central Nervous System Depressants; D012701:Serotonin; D000431:Ethanol