Effect of chronic tricylic antidepressant treatment on the serotoninergic autoreceptor: a microiontophoretic study in the rat.

Chronic treatment with tricyclic antidepressant (TCA) drugs has been shown to enhance the responsiveness of rat forebrain neurons to serotonin (5-HT). In the present study, imipramine (5 mg and 10 mg/kg), iprindole (2.5 mg/kg), desipramine and femoxetine (5 mg/kg) were administered daily for 14 days. The response of dorsal raphe neurons to intravenous injection of LSD (4 microgram/kg) and to microiontophoretic applications of 5-HT and LSD was assessed 24 h after the last dose. The responsiveness to intravenous LSD and the effectiveness of microiontophoretic applications of 5-HT and LSD were not altered by TCA drug pretreatments. Furthermore, the treatments did not change the mean firing rate of these 5-HT neurons. Those results suggest that chronic treatment with TCA drugs does not alter the sensitivity of the 5-HT autoreceptor. Thus, the effect of the previously reported increase of postsynaptic neuron responsiveness to 5-HT would not be dampened by a decreased activity of the presynaptic neurons.