Pharmacological evidence for a role of gamma-aminobutyric acid A receptor mechanism in modulating nitric oxide synthase activity in rat brain

The role of gamma -aminobutyric acid (GABA) mechanism on the synthesis of n itric oxide (NO) has been investigated by measuring the activity of nitric oxide synthase (NOS) and the concentration of NO in rat brain 15 min after administration of anticonvulsant doses of diazepam (0.25 and 0.5 mg/kg) whi ch is known to activate GABA A receptor for its anticonvulsant action. Diaz epam enhanced both NOS activity and the concentration of NO in a dose-depen dent manner. A reversal has been observed in animals treated with a convuls ant dose of picrotoxin (5 mg/kg) which is known to produce convulsions by b locking GABA A receptor mechanism. These results suggest that a functional interaction occurs between GABA A receptor activity and NO synthesis in the brain. (C) 2001 Elsevier Science Ltd. All rights reserved.