The combined effects of chronic ethanol/desipramine treatment on β-adrenoceptor density and coupling efficiency in rat brain

Abstract

Both ethanol and desipramine influence β-adrenoceptor regulation. We reported previously that ethanol partially counteracted desipramine's effects on β-adrenoceptor. Previous studies utilized β-adrenoceptor radioligands that also bind to 5-HT 1B receptors, thus, changes in 5-HT 1B receptors could have confounded the results. The effects of chronic ethanol, desipramine and ethanol/desipramine treatment on β-adrenoceptor coupling efficiency to G s protein in rat brain were examined using 125 I -iodocyanopindolol after blocking binding to 5-HT 1B receptors. In the frontal cortex, ethanol uncoupled β-adrenoceptor from G s. Desipramine decreased β-adrenoceptor 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 β-adrenoceptor coupling, but ethanol had no effect. In combination with desipramine, ethanol enhanced desipramine-induced decrease in β-adrenoceptor density in the high-conformational state, but uncoupled β-adrenoceptors, an effect not observed with ethanol alone. These results suggest a complex interplay between ethanol and antidepressants in modulating β-adrenoceptor function.