This study assessed the effects of central serotonergic depletion on exploratory activity at baseline, as well as after administration of d-amphetamine or the anxiogenic beta-carboline FG-7142. Intraventricular 5,7-dihydroxytryptamine (5,7-DHT) induced an almost complete depletion of serotonin [5-hydroxytryptamine (5-HT)] in the medial prefrontal cortex, nucleus accumbens, medial corpus striatum, and hippocampus with no changes in norepinephrine, dopamine or dihydroxyphenylacetic acid concentrations. 5-HT-depleted rats demonstrated reduced spontaneous and d-amphetamine-augmented exploration 3-10 weeks postoperatively. An effect on FG-7142-induced inhibition of exploratory activity was not apparent. These data implicate 5-HT systems in the expression of different aspects of exploratory and amphetamine-augmented motor behaviors.