Modulation of 5-HT1C receptors and phosphoinositide system by ethanol consumption in rat brain and choroid plexus.
The effect of chronic ethanol consumption (60 days) on 5-HT1C receptors as measured by [3H]mesulergine binding in the hippocampus, cortex, and choroid plexus of rats was investigated. The 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus was also investigated. It was observed that chronic ethanol treatment significantly increased the 5-HT-stimulated [3H]inositol 1-phosphate ([3H]IP1) formation, as well as the density (Bmax) of 5-HT1C receptors without causing a significant change in affinity (KD) of [3H]mesulergine binding in rat choroid plexus. It was also observed that chronic ethanol consumption had no significant effect on the Bmax or KD of 5-HT1C receptor binding sites in the hippocampus and cortex brain regions of rats. These results thus suggest that chronic ethanol consumption causes an up-regulation of both 5-HT1C receptors and 5-HT1C receptor-mediated phosphoinositide hydrolysis in rat choroid plexus but has no significant effects on the 5-HT1C receptors in brain. These results also suggest that 5-HT1C receptors and their functional response may be involved in the pathogenesis of alcohol dependence.
Pandey
S C
SC
Dept. of Psychiatry, College of Medicine, University of Illinois, Chicago.
Dubey
M P
MP
Piano
M R
MR
Schwertz
D W
DW
Davis
J M
JM
Pandey
G N
GN
D000818:Animals; D000978:Antiparkinson Agents / Q000378:metabolism; D001665:Binding Sites; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002831:Choroid Plexus / Q000187:drug effects* / Q000378:metabolism; D004873:Ergolines / Q000378:metabolism; D000431:Ethanol / Q000633:toxicity*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006868:Hydrolysis; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000978:Antiparkinson Agents; D004873:Ergolines; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D000431:Ethanol; C031649:mesulergine