The effect of repeated administration of antidepressant drugs on the responsiveness of rats to catecholamine agonists.

The antidepressant drugs, imipramine (10 mg/kg s.c.), amitriptyline (10 mg/kg s.c.), mianserin (2 mg/kg i.p.), danitracen (3 mg/kg i.p.) or the vehicle were administered to rats twice a day for 4 or 10 days. Clonidine (0.5 mg/kg s.c.) induced in rats chronically treated with the compounds studied an increase in locomotor activity but, at the same time, did not affect or decreased this activity in rats chronically treated with the vehicle or a single dose of an antidepressant. This refers, in particular, to imipramine, amitriptyline and danitracen which have a similar effect. This effect, an increase in motility, was most pronounced and common for all the three drugs (after a 4- and 10-day treatment) when clonidine was administered 72 hours after the last dose of an antidepressant. Only in a few cases the amphetamine-induced hypermotility was enhanced by a chronic administration of antidepressants (a 4-day amitriptyline treatment, 72 hours after the last injection; a 4-day mianserin or danitracen treatment, 48 hours after the last injection). The results obtained seem to suggest that a chronic administration of the antidepressant drugs may cause a change in the sensitivity of the central noradrenaline receptors.