Studies on the participation of the dopaminergic system in the central effects of chronically administered antidepressant drugs.
Spontaneous locomotor activity, sedative and stereotypic action of apomorphine, and utilization of noradrenaline and dopamine in the brain of rats treated chronically for 3 weeks with imipramine, amitriptyline, doxepine, and nomifensine ip were tested 1, 24, 48 and 72 h after the last administration of the drugs. The treatment did not change the locomotor activity, producing only slight sedation after 1 h, counteracted the sedation and potentiated the stereotypy induced by apomorphine, and increased the utilization of noradrenaline and dopamine after 48 h. It also antagonized the depressant action of apomorphine on dopamine utilization after 72 h. The results indicate the participation of dopamine in the mechanism of action of all investigated antidepressant drugs. They also suggest the depression of sensitivity of presynaptic dopamine receptors in the brain 48-72 h after cessation of antidepressant treatment.