Chronic antidepressant treatment reduces central beta-adrenoceptor sensitivity in a behavioural test.
The ability of beta-adrenoceptor agonists to potentiate the head-twitch response to 5-hydroxytryptophan (5-HTP) in mice was used to assess the in vivo sensitivity of beta-adrenoceptors 48 h after cessation of acute or chronic administration of desmethylimipramine (DMI) or iprindole (IPD). Neither acute nor chronic antidepressant administration significantly altered the head-twitch response to 5-HTP alone. Forty-eight hours after withdrawal from chronic but not acute pretreatment with DMI or IPD the potentiating effects of dobutamine, prenalterol and salbutamol were significantly decreased. This is consistent with a reduction in beta-adrenoceptor density and suggests that the 'spare' beta-adrenoceptor pool is small enough for this to result in functional subsensitivity. Implications of these findings are discussed.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D007488:Iprindole / Q000494:pharmacology; D008297:Male; D051379:Mice; D011294:Prenalterol / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects* / Q000502:physiology
D000928:Antidepressive Agents; D011943:Receptors, Adrenergic, beta; D004280:Dobutamine; D007488:Iprindole; D006916:5-Hydroxytryptophan; D011294:Prenalterol; D000420:Albuterol; D003891:Desipramine