Regulation of benzodiazepine receptor binding and GABAA subunit mRNA expression by punishment and acute alprazolam administration

Quantitative autoradiography of benzodiazepine (BZ) receptors and competitive reverse transcription-polymerase chain reaction were used to characterize changes in BZ binding and GABA(A) receptor subunit transcription levels associated with the anxiolytic effects of alprazolam. Effects were assessed on punished and non-suppressed water consumption using a lick suppression (Vogel) paradigm. Alprazolam had no effect on non-suppressed licking, [H-3]Ro 15-1788 binding or receptor subunit transcript levels, compared to non-drug controls. When each fifth lick produced a shock (0-0.5 mA), responding was suppressed in an intensity-related manner. The highest intensity significantly decreased licking (85%), [H-3]Ro 15-1788 binding (12%) and oil transcript levels (63%) in the basolateral nucleus of the amygdala, and [H-3]Ro 15-1788 binding in the mediodorsal thalamic nucleus (15%), compared to non-punished controls. Punishment increased the ratio of gamma 2L/S transcripts in the basolateral nucleus of the amygdala. Alprazolam blocked or reversed each of these effects. These results show that punishment has similar effects on BZ binding and GABA(A) receptor subunit expression and that alprazolam can block or reverse those effects. Such changes may be related to the anxiolytic effects of alprazolam. (C) 2000 Elsevier Science B.V. All rights reserved.