ANTIDEPRESSANT-INDUCED MODULATION OF GABA(A) RECEPTORS AND BETA-ADRENOCEPTORS BUT NOT GABA(B) RECEPTORS IN THE FRONTAL-CORTEX OF OLFACTORY BULBECTOMISED RATS
T. Dennis et al., ANTIDEPRESSANT-INDUCED MODULATION OF GABA(A) RECEPTORS AND BETA-ADRENOCEPTORS BUT NOT GABA(B) RECEPTORS IN THE FRONTAL-CORTEX OF OLFACTORY BULBECTOMISED RATS, European journal of pharmacology, 262(1-2), 1994, pp. 143-148
The effects of prolonged administration of antidepressant drugs, belon
ging to three different classes, on high-affinity GABA(A) receptor, GA
BA(B) receptor and beta-adrenoceptor binding parameters were determine
d in the frontal cortex of olfactory bulbectomised rats. Clorgyline (1
mg/kg/day), paroxetine (10 mg/kg/day) or desipramine (10 mg/kg/day) w
ere administered for 21 days via subcutaneous osmotic minipumps implan
ted in the scapular region 7 days after bulbectomy. Cortical GABA(A) r
eceptor densities, defined with [H-3]gamma-aminobutyric acid ([H-3]GAB
A), were significantly increased following bulbectomy. This effect on
B-max values was reversed by all three antidepressant drugs. GABA(B) r
eceptor densities decreased slightly after bulbectomy. Chronic antidep
ressant administration had no effect on GABA(B) receptor binding param
eters. Olfactory bulbectomy did not induce any changes in cortical bet
a-adrenoceptor binding parameters determined with [H-3]CGP-12177 ((-)-
4-(3-t-butylamino-2-hydroxypropoxy)- [5,7-H-3]benzimidazol-2-one). How
ever, prolonged administration of all three antidepressant drugs induc
ed a downregulation of beta-adrenoceptors. The results of the present
study confirm the involvement of cortical GABA(A) rather than GABA(B)
receptors in the olfactory bulbectomy animal model of human depression
. Moreover, the data further support the hypothesis that a decrease in
function of the GABA(A) receptor complex could play a role in the the
rapeutic effects of antidepressant treatments.