Antidepressant treatments, including sibutramine hydrochloride and electroconvulsive shock, decrease beta 1- but not beta 2-adrenoceptors in rat cortex.
The beta 1- and beta 2-adrenoceptor populations in rat cortex were individually quantified by labelling all of the receptors with [3H]dihydroalprenolol and displacing with isoprenaline (200 microM) or CGP 20712A (1-(2-[(3-carbamoyl-4-hydroxy)phenoxy]ethylamino)-3-[4-(1-methyl-4- trifluoromethyl-2-imidazolyl)phenoxy]-2-propanol methanesulphonate; 100 nM) to define total beta-adrenoceptors and beta 1-adrenoceptors, respectively. Binding parameters for beta 2-adrenoceptors were calculated by the difference. Oral administration of the monoamine reuptake inhibitors sibutramine HCl (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg), or zimeldine (10 mg/kg) for 10 days decreased the total number of beta-adrenoceptors present in rat cortex. This effect was entirely due to a reduction in the number of beta 1-adrenoceptors. Similarly, 10 days of treatment with the monoamine oxidase inhibitor tranylcypromine (10 mg/kg p.o.) or five electroconvulsive shocks (ECSs; 200 V, 2 s) spread over this period also down-regulated beta-adrenoceptors by reducing the content of the beta 1-subtype. By contrast, treatment with clenbuterol (5 mg/kg p.o.) for 10 days reduced the number of cortical beta-adrenoceptors by an effect on the beta 2-adrenoceptor population. The effects of short-term treatment with these drugs were also investigated, and, using the doses shown above, the results of 3 days of administration or a single ECS were determined. Sibutramine HCl and desipramine were alone in producing a reduction in number of beta-adrenoceptors after 3 days. Once again, this was exclusively due to a loss of beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Heal
D J
DJ
Research Department, Boots Company PLC, Nottingham, England.
Butler
S A
SA
Hurst
E M
EM
Buckett
W R
WR
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002976:Clenbuterol / Q000494:pharmacology; D003503:Cyclobutanes / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000378:metabolism; D004597:Electroshock; D007700:Kinetics; D008297:Male; D051381:Rats; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism*; D012016:Reference Values; D014191:Tranylcypromine / Q000494:pharmacology; D015031:Zimeldine / Q000494:pharmacology
D000928:Antidepressive Agents; D003503:Cyclobutanes; D011943:Receptors, Adrenergic, beta; D000639:Amitriptyline; D014191:Tranylcypromine; D015031:Zimeldine; D004082:Dihydroalprenolol; D003891:Desipramine; C058254:sibutramine; D002976:Clenbuterol