Differential effects of antidepressants on GABA B and β-adrenergic receptors in rat cerebral cortex

Abstract

The effects of chronic administration of antidepressant drugs on β-adrenergic and γ-aminobutyric 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/dy, and phenelzine (PLZ), 10 mg/kg/dy] were administered to male Sprague-Dawley rats by constant infusion via Alzet 2M L4 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 GABA B receptors was measured in frontal cortex and the remaining cortical tissue was used to measure [ 3H]dihydroalprenolol ([ 3H]DHA) binding to β-adrenoceptors. All drugs tested induced a significant decrease in density ( B max) of [ 3H]DHA binding, although no significant changes in affinity ( k d ) 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 K d were observed. These data do not support the proposal that an increase in the total population of cortical GABA B receptors is a common effect of chronic antidepressant treatment.