Serotonin1A receptor autoradiography during alcohol-withdrawal kindling

Abstract

A series of autoradiography experiments were conducted in order to test the theory that the serotonin (5-HT) receptor subtype 5-HT_1a is involved in alcohol-withdrawal kindled convulsive behaviour. Alcohol-withdrawal kindling was performed by subjecting male Wistar rats to multiple episodes consisting of 2 days of alcohol intoxication and 5 days of alcohol withdrawal. In the first episode alcohol intoxication led to focal downregulation of [³H]-8-hydroxy-2-(di-n-propylamino)tetralin ([³H]-8-OH-DPAT) binding sites in septum and subregions of frontal cortex, hippocampus, and entorhinal cortex. This alcohol-induced response was blunted in both alcohol-withdrawal kindled animals and in animals exposed to repeated alcohol dependence in which the previous withdrawal reactions were blocked by diazepam administration. A paradoxical upregulation of [³H]-8-OH-DPAT binding sites was found in septum and subregions of frontal cortex, hippocampus, and entorhinal cortex in control animals which were fed isocalorically with the alcohol-withdrawal kindled animals and subsequently exposed to 2 days of alcohol intoxication. It was concluded that the alterations in the alcohol induced 5-HT_1a receptor regulation after multiple episodes of alcohol dependence were not caused by alcohol-withdrawal kindling processes per se, but were due to both alcohol specific and alcohol non-specific effects.