Gnm. Gurguis et al., The combined effects of chronic ethanol/desipramine treatment on beta-adrenoceptor density and coupling efficiency in rat brain, EUR J PHARM, 363(2-3), 1998, pp. 241-251
Both ethanol and desipramine influence beta-adrenoceptor regulation. We rep
orted previously that ethanol partially counteracted desipramine's effects
on beta-adrenoceptor. Previous studies utilized beta-adrenoceptor radioliga
nds that also bind to 5-HT1B receptors, thus, changes in 5-HT1B receptors c
ould have confounded the results. The effects of chronic ethanol, desiprami
ne and ethanol/desipramine treatment on beta-adrenoceptor coupling efficien
cy to G(s) protein in rat brain were examined using I-125-iodocyanopindolol
after blocking binding to 5-HT1B receptors. In the frontal cortex, ethanol
uncoupled beta-adrenoceptor from G(s). Desipramine decreased beta-adrenoce
ptor density, particularly in the high-conformational state, with no effect
on coupling. In combined treatment, desipramine prevented ethanol-induced
uncoupling. In the hippocampus, desipramine enhanced beta-adrenoceptor coup
ling, but ethanol had no effect. In combination with desipramine, ethanol e
nhanced desipramine-induced decrease in beta-adrenoceptor density in the hi
gh-conformational state, but uncoupled beta-adrenoceptors, an effect not ob
served with ethanol alone. These results suggest a complex interplay betwee
n ethanol and antidepressants in modulating beta-adrenoceptor function. (C)
1998 Elsevier Science B.V. All rights reserved.