Enhancement of 5-hydroxytryptamine-induced behavioral effects following chronic administration of antidepressant drugs.

It has been shown recently that chronic administration of tricyclic antidepressant drugs results in enhanced responsiveness of neurones to iontophoretically applied 5-hydroxytryptamine (5-HT) in rat forebrain regions. The present investigation tested whether this efect is accompanied by an enhancement of behavioral effects of the amine. Behavioral signs of sleep in young chicks following systemic administration of 5-HT were used as an index of the acion of the amine at central receptor sites. Imipramine, desipramine, amitryptiline, pizotifen, and mianserin given 30 min before 5-HT all reduced the duration of 5-HT-induced behavioral depression. However, 6-8 day pretreatment with the same drugs resulted in an increased duration of the 5-HT-induced depression. The results suggest that the antidepressant drugs can block 5-HT receptors in the central nervous system (CNS) and that chronic blockade resulting from repeated administration of the drugs results in an increase in number or sensitivity of 5-HT receptors.