Allosteric modulation of GABAA receptor by somatostatin is altered under stress in rat brainstem

This study was conducted to investigate somatostatin modulation of GABAA receptor binding in several rat brainstem structures, located principally in the mesencephalon, after exposure to acute immobilization stress (single 1-hour session). Animals were randomly assigned to either control or stress conditions and changes in specific binding of the GABAA receptor as labelled with TBPS were assessed by in vitro quantitative autoradiography with the aid of a computer-assisted image analysis system. Exposure to immobilization stress led to a significant increase in [35S]TBPS binding site density in the SN of stressed rats compared to controls. In the other brainstem structures analysed, specific binding of [35S]TBPS remained unchanged in stressed rats. Furthermore, the results of the present in vitro study demonstrate an alteration of the modulatory effect of somatostatin on the GABAA receptor complex in the SN of stressed rats as compared to controls. This apparent alteration of allosteric effects of GABA receptor-somatostatin in the SN of stressed rats was eliminated in the presence of 1 micromolar concentration of GABA. Taken together, these data provide the first evidence of stress-induced alteration of allosteric effects of GABA-somatostatin in the rat mesencephalon. Furthermore, they also demonstrate that the tetradecapeptide somatostatin is particularly effective in modifying the [35S]TBPS binding to the GABAA receptor in this cerebral region.