CHRONIC TREATMENT WITH AMITRIPTYLINE ALTERS THE GABA-MEDIATED UPTAKE OF CL-36- IN THE RAT-BRAIN

Amitriptyline inhibits the GABA-mediated uptake of Cl-36- in membrane vesicles prepared from the cerebral cortices of drug-naive and saline-treated rats. In contrast, chronic in vivo treatment with amitriptyline affects an increase in the GABA-stimulated uptake of chloride ions in its presence. The benzodiazepine receptor antagonist ZK 93426 blocks the capacity of amitriptyline to augment the uptake of Cl-36- by 30-mu-M GABA. There is a possibility that there are two distinct effects of amitriptyline's action in the rat forebrain. The first is evident in vesicles from drug-naive animals and the second only after chronic treatment with this antidepressant. The authors discuss the pertinence of this finding to the mechanism of action of amitriptyline.