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.