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 reported previously that ethanol partially counteracted desipramine's effects on beta-adrenoceptor. Previous studies utilized beta-adrenoceptor radioligands that also bind to 5-HT1B receptors, thus, changes in 5-HT1B receptors could have confounded the results. The effects of chronic ethanol, desipramine and ethanol/desipramine treatment on beta-adrenoceptor coupling efficiency to Gs protein in rat brain were examined using 125I-iodocyanopindolol after blocking binding to 5-HT1B receptors. In the frontal cortex, ethanol uncoupled beta-adrenoceptor from GS. Desipramine decreased beta-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 beta-adrenoceptor coupling, but ethanol had no effect. In combination with desipramine, ethanol enhanced desipramine-induced decrease in beta-adrenoceptor density in the high-conformational state, but uncoupled beta-adrenoceptors, an effect not observed with ethanol alone. These results suggest a complex interplay between ethanol and antidepressants in modulating beta-adrenoceptor function.
Gurguis
G N
GN
Department of Veterans Affairs Medical Center, Dallas, TX 75216, USA. gurguis.george@dallas.va.gov
Turkka
J
J
Karanian
J
J
Linnoila
M
M
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D003891:Desipramine / Q000494:pharmacology*; D004347:Drug Interactions; D000431:Ethanol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D020120:Iodocyanopindolol / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*
D018759:Adrenergic Uptake Inhibitors; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002492:Central Nervous System Depressants; D011943:Receptors, Adrenergic, beta; D000431:Ethanol; D020120:Iodocyanopindolol; D007545:Isoproterenol; D003891:Desipramine