THE BENZODIAZEPINE RECEPTOR ANTAGONIST FLUMAZENIL INCREASES ACETYLCHOLINE-RELEASE IN RAT HIPPOCAMPUS

The benzodiazepine receptor antagonist flumazenil (2.5-20 mg/kg i.p.) increased acetylcholine (ACh) release by up to 85% in the hippocampus of freely moving rats. In contrast, the benzodiazepine receptor full agonist diazepam (2.5-10 mg/kg i.p.) decreased ACh release up to a maximum of 45% in the same brain area. Injection of flumazenil (10 pmol) or diazepam (10 pmol) into the medial septum increased (95%) or reduced (50%), respectively, ACh release in the hippocampus. The maximum effect produced by those drugs was of the same magnitude as that observed after systemic injection. The changes in hippocampal cholinergic function elicited by activation and blockade of benzodiazepine receptors in the medial septum may thus play a crucial role in the alterations of the cognitive processes elicited by benzodiazepine receptor ligands.