Chronic treatment with amitriptyline alters the GABA-mediated uptake of 36Cl- in the rat brain.
Amitriptyline inhibits the GABA-mediated uptake of 36Cl- 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 36Cl- by 30 microM 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.
Malatynska
E
E
Department of Pharmacology, University of Arizona Tucson 85724.
Giroux
M L
ML
Dilsaver
S C
SC
Schwarzkopf
S B
SB
D000639:Amitriptyline / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002243:Carbolines / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D002713:Chlorine; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D002243:Carbolines; D002712:Chlorides; D011868:Radioisotopes; D011963:Receptors, GABA-A; D000639:Amitriptyline; D002713:Chlorine; D005680:gamma-Aminobutyric Acid; C042568:ZK 93426