Imipramine and desipramine decrease the GABA-stimulated chloride uptake, and antigabaergic agents enhance their action in the forced swimming test in rats.
The present study reports that long-term (18 days) administration of imipramine (IMI, 20 mg/kg) or desipramine (DMI, 15 mg/kg) produced a significant decrease in the GABA-stimulated 36Cl- uptake into membrane vesicles from the cerebral cortex of rats (experiment 1). Experiments 2A, B show that anti-immobility effects of DMI and IMI (subacute treatment) in the forced swimming test are enhanced when a single subconvulsant injection of picrotoxin or pentylenetetrazol is administered to the animals concurrently to the last antidepressant injection. These results are discussed in relation with a current GABAergic hypothesis of depression and antidepressant drug action.
Fernández-Teruel
A
A
Department of Pharmacology and Psychiatry, School of Medicine, Autonomous University of Barcelona, Spain.
Escorihuela
R M
RM
Boix
F
F
Longoni
B
B
Corda
M G
MG
Tobeña
A
A
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D002713:Chlorine; D003863:Depression / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology*; D018756:GABA Antagonists; D007099:Imipramine / Q000494:pharmacology*; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology; D011868:Radioisotopes; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000502:physiology; D013550:Swimming; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D002712:Chlorides; D002713:Chlorine; D003891:Desipramine; D018756:GABA Antagonists; D007099:Imipramine; D010433:Pentylenetetrazole; D010852:Picrotoxin; D011868:Radioisotopes; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid