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

• Published in: European journal of pharmacology 1998-12, Vol.363 (2), p.241-251
• Main Authors: Gurguis, George N.M, Turkka, Jukka, Karanian, John, Linnoila, Markku
• Format: Article
• Language: English
• Subjects: Adrenergic beta-Agonists - pharmacology; Adrenergic beta-Antagonists - pharmacology; Adrenergic Uptake Inhibitors - pharmacology; Alcoholism; Alcoholism and acute alcohol poisoning; Animals; Antidepressant; Binding, Competitive; Biological and medical sciences; Brain - drug effects; Brain - metabolism; Central Nervous System Depressants - pharmacology; Cerebral Cortex - drug effects; Cerebral Cortex - metabolism; Coupling; Depression; Desipramine; Desipramine - pharmacology; Drug Interactions; Ethanol; Ethanol - pharmacology; G s protein; Hippocampus - drug effects; Hippocampus - metabolism; Iodocyanopindolol - pharmacology; Isoproterenol - pharmacology; Male; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Sprague-Dawley; Receptors, Adrenergic, beta - drug effects; Receptors, Adrenergic, beta - metabolism; Toxicology
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(98)00810-3

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.