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

The β1 and β2‐adrenoceptor populations in rat cortex were individually quantified by labelling all of the receptors with [3H]dihydroalprenolol and displacing with iso‐prenaline (200 μM) or CGP 20712A (l‐{2‐[(3‐carbamoyl‐4‐hydroxy)phenoxy]ethylamino}‐3‐[4‐(l‐methyl‐4‐trifluoro‐methyl‐2‐imidazolyl)phenoxy]‐2‐propanol methanesul‐phonate; 100 nM) to define total β‐adrenoceptors and β1‐adrenoceptors, respectively. Binding parameters for β2‐adrenoceptors were calculated by the difference. Oral administration of the monoamine reuptake inhibitors sibutramine HC1 (3 mg/kg), amitriptyline (10 mg/kg), desipramine (10 mg/kg), or zimeldine (10 mg/kg) for 10 days decreased the total number of β‐adrenoceptors present in rat cortex. This effect was entirely due to a reduction in the number of β1‐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 β‐adrenoceptors by reducing the content of the βsubtype. By contrast, treatment with clenbuterol (5 mg/kg p.o.) for 10 days reduced the number of cortical β‐adrenoceptors by an effect on the β2‐adre‐noceptor 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 HC1 and desipramine were alone in producing a reduction in number of β‐adrenoceptors after 3 days. Once again, this was exclusively due to a loss of β1‐adrenoceptors. Together, the results show that antidepressants with disparate pharmacological actions all down‐regulated β‐adrenoceptors through the neuronal β1‐adrenoceptor subtype. In addition, sibutramine HC1 and desipramine produced this attenuation very rapidly. However, clenbuterol treatment reduced the number of β2‐adrenoceptors, and its reported antidepressant activity is, therefore, unlikely to be mediated via this mechanism.