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

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.