Manipulations of 5-HT activity and memory in the rat.

The activity of 5-HT was manipulated by means of the peripheral injection of 5-HT reuptake inhibitors, fenfluramine and fluoxetine. These drug treatments, at doses higher than 1 mg/kg, produced retrograde amnesia in a one-trial appetitive learning task in rats. A non-specific inhibitor of 5-HT reuptake, imipramine, did not produce this amnesic effect, nor did the combination of fenfluramine with the MAOI tranylcypromine, although it produced, as expected, the "serotonergic syndrome." Results for the metabolic precursor of 5-HT, 5-HTP, also administered peripherally, were inconsistent, with amnesic effects seen at 5 and 20 mg/kg but none at 10 mg/kg.