Autoradiographic analysis of 5-hydroxytryptamine 5-HT2A binding sites in the rat brain after chronic intragastric ethanol treatments.
Several evidences indicate altered regulation of brain serotonergic mechanisms in alcohol abuse; changes in 5-HT2A receptor density and functioning have been observed in several lines of alcohol-preferring rats. Using quantitative autoradiography, the present study investigated the influence of chronic intragastric ethanol treatment on forebrain 5-HT2A binding sites in rats. Administration for 7 days of high doses of ethanol, which induced physical dependence, lowered the levels of 5-HT2A binding sites in the cingulate cortex, the frontal cortex and in the agranular insular cortex. The effect was observed immediately after the last ethanol administration, was statistically significant 14 h later, when marked withdrawal signs were observed, and remained significant after 8 days of detoxification, when withdrawal signs were no longer evident. No significant differences were detected in the claustrum, parietal cortex, piriform cortex, caudate putamen, olfactory tubercle, nucleus accumbens, shell and core. Chronic treatment with 6 g/kg of ethanol, which did not induce dependence, did not modify 5-HT2A binding sites. These long-lasting changes in brain 5-HT2A binding sites observed in the present study might contribute to specific aspects of ethanol dependence, such as development of depression and alcohol craving.
Fedeli
Amalia
A
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, 62032 Camerino, (MC) Italy.
Ciccocioppo
Roberto
R
Economidou
Daina
D
Angeletti
Stefania
S
Massi
Maurizio
M
D000818:Animals; D001345:Autoradiography; D001665:Binding Sites / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D007441:Intubation, Gastrointestinal; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000378:metabolism; D013375:Substance Withdrawal Syndrome / Q000523:psychology
D002492:Central Nervous System Depressants; D044402:Receptor, Serotonin, 5-HT2A; D012702:Serotonin Antagonists; D000431:Ethanol; D007650:Ketanserin