CHRONIC ALCOHOLIZATION ALTERS THE EXPRESSION OF 5-HT1A AND 5-HT1B RECEPTOR SUBTYPES IN RAT-BRAIN

The expression of central 5-HT1A and 5-HT1B receptors was studied in s everal brain areas of rats subjected to a 2-week period of chronic alc oholization, followed by 18 h withdrawal. Quantitative autoradiography indicated that the ethanol treatment provoked an increase (similar to + 30%) in the labeling by [H-3]8-hydroxy-2-(di-n-propylamino)tetralin ([H-3]8-OH-DPAT) and [H-3]N-[2-[4-(2-methoxyphenyl)- 1-piperazinyl]et hyl]-N-(2-pyridinyl) cyclohexane carboxamide ([H-3]WAY-100635) of 5-HT 1A autoreceptors in the dorsal raphe nucleus, accompanied by a concomi tant decrease in the labeling of postsynaptic 5-HT1A receptors in the hippocampus (similar to - 20%), anterior (similar to - 30%) and poster ior (similar to - 32%) cortices. These changes were associated with a tendency toward an increase and decrease in 5-HT1A mRNA levels in the anterior raphe area and hippocampus, respectively, suggesting that the changes observed are due to modifications in 5-HT1A receptor protein synthesis. The autoradiographic labeling of 5-HT1B receptors by tonin- O-carboxymethylglycyl[I-125]iodotyrosinamide ([I-125]GTI) was found to increase ( + 55 %) in the globus pallidus of alcoholized rats. Intere stingly, a significant increase (+ 57%) in S-HT1B receptor mRNA levels was observed in the striatum, which contains cell bodies of neurons p rojecting into the globus pallidus. These data suggest that altered se nsitivity of chronically alcoholized rats to 5-HT1A and 5-HT1B recepto r ligands may result from alcohol-induced changes in the transcription of the genes encoding these receptors.