Effects of 5-HT receptor subtype-selective drugs on locomotor activity and motor habituation in the DHT adult rat model.
5-Hydroxytryptophan (5-HTP) induces biphasic time and dose dependent effects on locomotor activity (LMA) and motor habituation in rats with 5,7-dihydroxytryptamine (DHT) lesions. To identify the role of serotonin (5-HT) receptors in these responses, we studied the effects of 5-HT2 receptor antagonists on LMA occurring spontaneously and evoked by 5-HTP or putative selective 5-HT agonists in rats injected intracisternally with DHT or vehicle. Motor habituation was assessed by analysis of computer-tabulated 10 minute "bins" during hour long recording. Neuroleptic 5-HT2 antagonists prevented 5-HTP stimulation of LMA in DHT-lesioned rats in the rank order of potency pirenperone greater than pipamperone greater than ketanserin = cinanserin. The non-neuroleptic ritanserin, however, did not reduce LMA stimulated by the 5-HT1B agonist RU24969 but did reverse transient suppression of LMA induced by high dose 5-HTP and by the putative 5-HT2 agonist DOI. RU24969, like 5-HTP, induced a failure of motor habituation which differed from DOI-evoked alteration. 8-OH-DPAT did not affect motor habituation at the dose tested. These data suggest that the 5-HT1B site mediates 5-HTP-evoked locomotor hyperactivity in the DHT model, that the 5-HT2 site participates in the transient hypoactivity seen with high doses of 5-HTP, and that 5-HT1 and 5-HT2 sites may be functionally linked. Both sites differentially influence motor habituation, which appears to be under complex regulation. Bin analysis is a sensitive index of these habituation effects.
D015116:5,7-Dihydroxytryptamine; D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D006185:Habituation, Psychophysiologic / Q000187:drug effects*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D016713:Ritanserin; D012701:Serotonin / Q000031:analogs & derivatives; D012702:Serotonin Antagonists / Q000494:pharmacology*
D010880:Piperidines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D016713:Ritanserin; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D006916:5-Hydroxytryptophan