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Antidepressant Treatments, Including Sibutramine Hydrochloride and Electroconvulsive Shock, Decrease β 1 but Not β 2 ‐Adrenoceptors in Rat Cortex
Author(s) -
Heal D. J.,
Butler S. A.,
Hurst E. M.,
Buckett W. R.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb07389.x
Subject(s) - antidepressant , electroconvulsive shock , electroconvulsive therapy , anesthesia , cortex (anatomy) , pharmacology , medicine , chemistry , neuroscience , psychology , hippocampus
The β 1 and β 2 ‐adrenoceptor populations in rat cortex were individually quantified by labelling all of the receptors with [ 3 H]dihydroalprenolol and displacing with iso‐prenaline (200 μ M ) 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 n M ) to define total β‐adrenoceptors and β 1 ‐adrenoceptors, respectively. Binding parameters for β 2 ‐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 β 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 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 β 2 ‐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 β 1 ‐adrenoceptors. Together, the results show that antidepressants with disparate pharmacological actions all down‐regulated β‐adrenoceptors through the neuronal β 1 ‐adrenoceptor subtype. In addition, sibutramine HC1 and desipramine produced this attenuation very rapidly. However, clenbuterol treatment reduced the number of β 2 ‐adrenoceptors, and its reported antidepressant activity is, therefore, unlikely to be mediated via this mechanism.