Chronic alcoholization alters the expression of 5-HT_1A and 5-HT_1B receptor subtypes in rat brain

The expression of central 5-HT_1A and 5-HT_1B receptors was studied in several brain areas of rats subjected to a 2-week period of chronic alcoholization, followed by 18 h withdrawal. Quantitative autoradiography indicated that the ethanol treatment provoked an increase (∼ + 30%) in the labeling by [³H]8-hydroxy-2-(di-n-propylamino)tetralin ([³H]8-OH-DPAT) and [³H]N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl) cyclohexane carboxamide ([³H]WAY-100635) of 5-HT_1A autoreceptors in the dorsal raphe nucleus, accompanied by a concomitant decrease in the labeling of postsynaptic 5-HT_1A receptors in the hippocampus (∼ -20%), anterior (∼ -30%) and posterior (∼ -32%) cortices. These changes were associated with a tendency toward an increase and decrease in 5-HT_1A mRNA levels in the anterior raphe area and hippocampus, respectively, suggesting that the changes observed are due to modifications in 5-HT_1A receptor protein synthesis. The autoradiographic labeling of 5-HT_1B receptors by serotonin-O-carboxymethylglycyl[¹²⁵I]iodotyrosinamide ([¹²⁵I]GTI) was found to increase (+55%) in the globus pallidus of alcoholized rats. Interestingly, a significant increase (+57%) in 5-HT_1B receptor mRNA levels was observed in the striatum, which contains cell bodies of neurons projecting into the globus pallidus. These data suggest that altered sensitivity of chronically alcoholized rats to 5-HT_1A and 5-HT_1B receptor ligands may result from alcohol-induced changes in the transcription of the genes encoding these receptors.