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.