Down-regulation of rat beta-adrenoceptors by clenbuterol or desipramine does not require chronic treatment: [3H] CGP-12177 binding reveals rapid (24 hour) modulation.
Desipramine (DMI, 15 mg/kg, s.c.) decreased [3H]CGP-12177-labelled cortical beta-adrenoceptor density (Bmax) by 30% upon chronic (14 day) treatment. However, even a single dose (in mg/kg) of DMI (15) or the beta-adrenoceptor agonist, clenbuterol (20), induced a rapid (24 hour) and significant reduction of beta-adrenoceptor Bmax (-15%; p < 0.01). Acute treatment with amitryptiline (10), clorgyline (1), fluoxetine (10), nomifensine (10) or maprotiline (20) had no significant effect on [3H]CGP-12177-labelled beta-adrenoceptors, suggesting that rapid down-regulation may not be a general property of antidepressant drugs. None of the antidepressants altered the Bmax of [3H]ketanserin-labelled 5-HT2A receptors on acute treatment. These results show that beta-adrenoceptor down-regulation by clenbuterol and DMI is not dependent on chronic treatment and may, therefore, be a poor correlate of the gradual onset of therapeutic efficacy seen clinically with antidepressant drugs.
Newman-Tancredi
A
A
Department of Psychopharmacology, Institut de Recherches Servier, Paris, France.
Verrièle
L
L
Chaput
C
C
Millan
M J
MJ
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000493:pharmacokinetics; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D002976:Clenbuterol / Q000494:pharmacology*; D003891:Desipramine / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects*; D008297:Male; D011412:Propanolamines / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000187:drug effects
D018759:Adrenergic Uptake Inhibitors; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018687:Antidepressive Agents, Second-Generation; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; D011985:Receptors, Serotonin; C033394:CGP 12177; D003891:Desipramine; D002976:Clenbuterol