Discriminative stimulus properties of L-5-hydroxytryptophan: behavioral evidence for multiple serotonin receptors.

Rats were trained to discriminate the stimulus properties of L-5-hydroxytryptophan (L-5-HTP) (30 mg/kg SC), the immediate precursor of serotonin (5-HT). The peripheral decarboxylase inhibitor R04-4602, administered prior to L-5-HTP, greatly attenuated the disruptive effects observed on responding when L-5-HTP alone was injected. Following acquisition, the discrimination was dose-dependent and generalized to fenfluramine, a 5-HT-releasing drug, but not to amphetamine, a catecholamine-releasing agent. Further evidence for the involvement of 5-HT receptor stimulation in mediating the discrimination was that pretreatment with fluoxetine, a highly specific 5-HT uptake inhibitor, markedly potentiated the cue. Nevertheless, the classical 5-HT antagonists methysergide, cyproheptadine, metergoline, and methiothepin did not block the L-5-HTP-related discriminative stimulus. This finding suggested that the cue properties of L-5-HTP might be mediated by a population of 5-HT receptors previously identified electrophysiologically in limbic structures. As in the present experiment, the putative 5-HT antagonists did not block the synaptic effects of 5-HT in these structures.