Effects of serotonin-selective and classical antidepressants on the auditory P300 cognitive potential

The cognitive potential, P300, is a phenomenon frequently studied in relati on to template matching of the brain. To understand the neurochemical mecha nisms of its generation, we compared the effects of three antidepressants, fluoxetine, tianeptine and clomipramine after single and repeated applicati on as well as after 1 week of withdrawal on the P300 and N200 waves in an a uditory 'odd-ball' paradigm in three parallel groups of 10 healthy voluntee rs. Following single administration, both fluoxetine and clomipramine reduc ed (-39 +/- 14%, p < 0.01) the peak amplitude of P300 at the Pt electrode. For fluoxetine and tianeptine, reduced amplitudes of 19 +/- 7% and 24 +/- 1 1%, respectively, were found following 8 days of treatment, 2 h after admin istration. However, for clomipramine no additional diminution was found on day 8 with respect to day 1. Topographic distributions tended to be signifi cantly modified at the frontal scalp area 1 h after the tianeptine administ ration on day 8, whereas the post-closing changes induced by fluoxetine wer e localised in the midline and right centrotemporal scalp regions. Only min or reductions in peak latencies have been observed. It can be concluded tha t serotonin selective drugs have a slower onset of P300 amplitude decrease than clomipramine, which has additional effects on monoaminergic and on cho linergic systems. These results suggest that serotonin has a regulatory fun ction in the neurotransmission of cerebral structures which are involved in the evaluation of stimulus relevance.