Functional supersensitivity to the alpha 1-adrenoceptor agonist after repeated treatment with antidepressant drugs is not conditioned by beta-down-regulation.
The effect of repeated administration of desipramine, and the (+)- and (-)-enantiomers of oxaprotiline (10 mg/kg i.p., twice daily for 14 days) on the binding of beta- and alpha 1-adrenoceptors in the cortex of the rat brain were studied. The functional consequences of such treatment were measured in a behavioural model, involving the exploratory activity of rats in response to administration of the alpha 1-agonist phenylephrine. Desipramine and (+)-oxaprotiline decreased the binding of [3H]dihydroalprenolol ([3H]DHA) to beta-adrenoceptors in the cortex, did not change the binding of [3H]prazosin to alpha 1-adrenoceptors, but enhanced behavioural responses to phenylephrine. A behavioural facilitation was also observed after administration of (-)-oxaprotiline, a substance which does not change the binding of [3H]DHA. These results indicate that a functional supersensitivity to the alpha 1-adrenoceptor agonist, after repeated treatment with antidepressants is not conditioned by beta-down-regulation.
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D003891:Desipramine / Q000494:pharmacology; D004082:Dihydroalprenolol; D008297:Male; D008376:Maprotiline / Q000031:analogs & derivatives / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D008376:Maprotiline; C027299:hydroxymaprotilin; D004082:Dihydroalprenolol; D003891:Desipramine; D011224:Prazosin