Down-regulation of serotonin2, but not of beta-adrenergic receptors during chronic treatment with amitriptyline is independent of stimulation of serotonin2 and beta-adrenergic receptors.
Antidepressant drugs down-regulate beta-adrenergic, alpha 2-adrenergic and serotonergic 5-HT2 receptors with a time course that parallels their clinical efficacy, i.e. chronic administration is required (Crews and Smith, 1978; Svensson and Usdin, 1978; Banerjee, Kung, Riggi and Chanda, 1979; Bergstrom and Keller, 1979; Peroutka and Snyder, 1980). In the present study, it was found that the 5-HT2 receptor antagonist, nefazadone (50 mg/kg per day) did not prevent the downregulation of 5-HT2 receptors in the cerebral cortex produced by amitriptyline (10 mg/kg per day), when administered for 3 weeks. Moreover, treatment with nefazadone (50 mg/kg per day) alone for 3 weeks decreased binding to 5-HT2 receptors in cerebral cortex. In contrast, administration of propranolol, the beta receptor antagonist, (10 mg/kg per day) with amitriptyline (10 mg/kg per day) for 3 weeks prevented the down-regulation of beta receptors, but did not alter the decrease in binding to 5-HT2 receptors. In addition, the depletion of central stores of norepinephrine and serotonin by a 4-day treatment with reserpine (5 mg/kg per day) increased binding to beta receptors in the cerebral cortex and hippocampus, but did not affect binding to 5-HT2 receptors in either region. These results suggest that the 5-HT2 receptor is not down-regulated by direct stimulation by serotonin agonists and that the down-regulation of 5-HT2 receptors by amitriptyline is independent of down-regulation of beta-adrenergic receptors.
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D004082:Dihydroalprenolol; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D010879:Piperazines; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology*; D013134:Spiperone / Q000378:metabolism; D014230:Triazoles / Q000494:pharmacology
D010879:Piperazines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; D014230:Triazoles; D000639:Amitriptyline; D012701:Serotonin; D013134:Spiperone; C051752:nefazodone; D004082:Dihydroalprenolol; D012110:Reserpine; D011433:Propranolol