Additional evidence that L-5-hydroxytryptophan discrimination models a unique serotonin receptor.
The purpose of the present studies was to investigate further the role of central serotonin (5-HT) in mediating the L-5-hydroxytryptophan (L-5-HTP) discriminative cue. Rats were trained to discriminate the stimulus properties of 35 mg/kg L-5-HTP combined with RO 4-4602, a peripheral decarboxylase inhibitor. Considering that several 5-HT antagonists were unable to block the L-5-HTP discriminative cue in our earlier studies, we extended these studies to include the two other presumed 5-HT antagonists mianserin and BC-105 (pizotyline). Only BC-105 completely blocked the training dose of L-5-HTP. Furthermore, the blockade of the L-5-HTP cue was both graded and surmountable by increasing the dose of L-5-HTP, suggesting a competitive antagonism. In neurochemical studies, the regional brain levels of 5-HT, norepinephrine and dopamine were determined after the injection of the training dose of L-5-HTP. Marked changes in the levels of 5-HT were found, while the levels of the catecholamines were changed only slightly or not at all. Furthermore, dose-response studies of L-5-HTP demonstrated an orderly dose-related increase in the levels of 5-HT in brain and in the percent responding on the L-5-HTP lever, while no such relationship was found for brain catecholamines. These results agree with previous pharmacological studies and suggest that the L-5-HTP discrimination is mediated by a central 5-HT receptor that has pharmacological properties distinct from those receptors identified in previous behavioral models of 5-HT receptor stimulation.
D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D008803:Mianserin / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000378:metabolism; D010918:Pizotyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*
D018377:Neurotransmitter Agents; D011985:Receptors, Serotonin; D010918:Pizotyline; D008803:Mianserin; D006916:5-Hydroxytryptophan