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)