Effects of chronic antidepressant treatment on beta-adrenoceptor subtype binding in the rat cerebral cortex and cerebellum.
The effects of desipramine, tranylcypromine, and phenelzine on beta-adrenoceptor subtype binding were measured in rat cerebral cortex and cerebellum. The drugs were administered to male Sprague Dawley rats for 28 d sc via 2ML4 Alzet osmotic minipumps (desipramine HCl 10, tranylcypromine HCl 1, phenelzine sulfate 5, 10 mg kg-1/d). Binding of [3H]CGP 12177 was measured to determine total beta-adrenoceptor density in each brain region. The relative densities of beta 1- and beta 2-adrenoceptors were directly calculated from competition analysis using ICI 89406 to displace [3H]CGP 12177. beta 1-Adrenoceptor density was decreased in cortical tissue following each antidepressant treatment, but no effects on beta 2-adrenoceptor density were evident. With cerebellar tissue, despite a higher density of beta 2-adrenoceptors in this area, no effects of antidepressants on beta 2-adrenoceptor density were evident. The present data confirm and extend previous reports of beta 1- but not beta 2-adrenoceptor downregulation in brain following chronic antidepressant drug treatment.
Paetsch
P R
PR
Department of Psychiatry, University of Alberta, Edmonton, Canada.
Greenshaw
A J
AJ
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003891:Desipramine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D010624:Phenelzine / Q000494:pharmacology; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects; D014191:Tranylcypromine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D000928:Antidepressive Agents; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D014191:Tranylcypromine; D010624:Phenelzine; C033394:CGP 12177; D003891:Desipramine