THE BENZODIAZEPINE ANTAGONIST CGS-8216 PREVENTS HYPERAMMONEMIA-INDUCED SOMATOSTATIN RECEPTOR REDUCTION IN THE BRAIN

Previous results from our group showed that hyperammonemia decreases t he number of somatostatin (SS) receptors and that benzodiazepine recep tors might regulate the number of SS receptors in rat brain. These fin dings together with the supersensitivity of benzodiazepine receptors i n the hyperammonemic rat brain suggest that benzodiazepine receptors m ight mediate the effect of hyperammonemia on SS receptors. To assess t his hypothesis we tested whether 2-phenylpyrazolo[3, 4-c]-quinolin-3(5 H)-one (CGS 8216), a benzodiazepine antagonist, prevented the effect o f ammonium acetate on rat brain SS receptors. Administration of ammoni um acetate (5 mmol/kg, i.p.) for 7 days did not affect the levels of s omatostatin-like immunoreactivity but decreased the number of SS recep tors in synaptosomes from the frontoparietal cortex and hippocampus wi thout affecting their apparent affinity. This decrease could be blocke d by the concomitant administration of CGS 8216 (10 mg/kg, i.p.). The benzodiazepine antagonist alone had no observable effect on the somato statinergic system. These results suggested that the effect of hyperam monemia on SS receptors could be mediated, at least in part, through t he benzodiazepine receptors.