Antidepressant Treatments, Including Sibutramine Hydrochloride and Electroconvulsive Shock, Decrease β1 but Not β2‐Adrenoceptors in Rat Cortex

Abstract

The .beta.1- and .beta.2-adrenoceptor populations in rat cortex were individually quantified by labelling all of the receptors with [3H]dihydrdoalprenolol and displacing with isoprenaline (200 .mu.M) or CGP 207 12A (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. Together, the results show that antidepressants with disparate pharmacological actions all down-regulated .beta.-adrenoceptors through the neuronal .beta.1-adrenoceptor subtype. In addition, sibutramine HCl and desipramine produced this attenuation very rapidly. However, clenbuterol treatment reduced the number of .beta.2-adrenoceptors, and its reported antidepressant activity is, therefore, unlikely to be mediated via this mechanism.