Differential effects of antidepressants on GABAB and beta-adrenergic receptors in rat cerebral cortex.
The effects of chronic administration of antidepressant drugs on beta-adrenergic and gamma-amino-butyric acid (GABA)B receptors have been assessed with radioligand binding. Tricyclics [imipramine (IMI), 30 mg/kg/day, and desmethylimipramine (DMI), 10 mg/kg day] or monoamine oxidase inhibitors [(+/-)-tranylcypromine (TCP), 1 mg/kg/day, and phenelzine (PLZ), 10 mg/kg/day] were administered to male Sprague-Dawley rats by constant infusion via Alzet 2ML4 osmotic minipumps for 28 days. Pumps were implanted s.c. in the interscapular region. On day 28 the animals were killed and their brains removed; [3H]GABA binding to GABAB receptors was measured in frontal cortex and the remaining cortical tissue was used to measure [3H]dihydroalprenolol ([3H]DHA) binding to beta-adrenoceptors. All drugs tested induced a significant decrease in density (Bmax) of [3H]DHA binding, although no significant changes in affinity (Kd) were observed. [3H]GABA binding was not altered significantly by chronic antidepressant treatment. TCP-treated animals showed a tendency towards increased [3H]-GABA binding, but the differences did not reach statistical significance. No effects on Kd were observed. These data do not support the proposal that an increase in the total population of cortical GABAB receptors is a common effect of chronic antidepressant treatment.
McManus
D J
DJ
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Greenshaw
A J
AJ
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects*; D004082:Dihydroalprenolol / Q000378:metabolism / Q000494:pharmacology; D005625:Frontal Lobe / Q000187:drug effects; D058787:GABA-A Receptor Antagonists; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D058787:GABA-A Receptor Antagonists; D008996:Monoamine Oxidase Inhibitors; D011943:Receptors, Adrenergic, beta; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid; D004082:Dihydroalprenolol