Repeated Treatment with Antidepressant Drugs: Responses Mediated by Brain Dopamine Receptors

Abstract

The therapeutic effect of antidepressant drugs (AD) in patients appears after about two weeks of treatment, and not immediately after the administration of a single dose. Such a latency period is observed for virtually all AD and is independent of the mechanism of action in the acute experiment. Therefore, it is justifiable to study the mechanism of antidepressant action in animals treated repeatedly with these drugs. In past years, the pharmacological and biochemical effects of repeated (not single-dose) administration of AD have been described in relation to a number of neurotransmitter systems or receptors (see Charney et al. 1981; Maj et al. 1984a). We have recently concentrated upon studying the effect of AD, given repeatedly, on the dopamine brain systems; this relationship has not yet been sufficiently examined (see Discussion). We used typical and atypical AD with different profiles revealed in the acute experiment, given, as a rule, in a dose of 10 mg/kg per orally, twice a day for 14 days. Pharmacological responses considered to be mediated by dopamine brain receptors — locomotor activity, exploratory behavior, stereotypy — were studied. Biochemical experiments (binding to dopamine receptors, levels of dopamine and its metabolites) were also carried out. The results of these studies are reviewed in this paper.