Autoradiographic analysis of 5-HT2A binding sites in the brain of Sardinian alcohol-preferring and nonpreferring rats.
The density of 5-HT2A binding sites in the brain of Sardinian alcohol-preferring (sP) and nonpreferring (sNP) rats was evaluated, using [3H]ketanserin for quantitative autoradiography. The highest [3H]ketanserin binding levels were found in the anterior olfactory nucleus, prefrontal cortex, medial prefrontal cortex, post-genual anterior cingulate cortex, insular cortex and claustrum. Statistically significant differences between sP and sNP rats were found in prefrontal cortex, medial prefrontal cortex and post-genual anterior cingulate cortex, where sP rats showed about 20% lower [3H]ketanserin binding levels. No significant difference was found in other areas, although some of them showed slightly lower [3H]ketanserin binding density in sP rats. The 5-HT2A receptor agonist, (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane hydrochloride (DOI), microinjected into the medial prefrontal cortex, induced a lower number of wet dog shakes in sP than in sNP rats. These results indicate a different density of 5-HT2A binding sites, and a different functional regulation of 5-HT2A receptor mechanisms in discrete brain areas of sP, in comparison to sNP rats. These findings, and those showing lower levels of 5-HT in the frontal cortex of sP rats, suggest that altered 5-HT function in fronto-cortical areas could be linked to the genetic predisposition to high voluntary ethanol intake in these rats.
Department of Pharmacological Sciences and Experimental Medicine, University of Camerino, Italy. massi@cambio.unicam.it
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Ciccocioppo
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Angeletti
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Colombo
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Gessa
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Massi
D000428:Alcohol Drinking / Q000235:genetics; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001345:Autoradiography; D001522:Behavior, Animal / Q000187:drug effects; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000737:chemistry / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014316:Tritium
D000662:Amphetamines; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D014316:Tritium; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine