Actions of 5-hydroxytryptophan to inhibit and disinhibit mouse behaviour in the light/dark test.
The involvement of 5-HT receptors in behavioural responding to an aversive situation was investigated in the mouse light/dark test. The administration of 5-hydroxytryptophan (5-HTP) (12.5-50 mg/kg i.p.) increased brain 5-HT turnover and inhibited mouse behaviour in the light/dark test box. The 5-HT2C/5-HT2A receptor antagonists methysergide (1.0 and 5.0 mg/kg i.p.) and ritanserin (0.1-1.0 mg/kg i.p.) antagonised (methysergide) or reversed (ritanserin) the effects of 5-HTP to an increased exploration of the light compartment; a low dose of the 5-HT3 receptor antagonist ondansetron (0.01 mg/kg i.p.) had a similar effect. The disinhibitory effect of the 5-HTP/ritanserin interaction was antagonised by the 5-HT3/5-HT4 receptor antagonists SDZ205-557 (0.001-0.1 mg/kg) and a high dose of tropisetron (1.0 mg/kg i.p.) but not by ondansetron (1.0 mg/kg i.p.). At these doses tropisetron and ondansetron had no effect in their own right. Thus the dominant effect of 5-HTP in the mouse is to inhibit behaviour, a response mediated via 5-HT2C/5-HT2A and 5-HT3 receptors. A 5-HT4 receptor may effect an opposing disinhibitory potential as revealed by ritanserin.
Cheng
C H
CH
School of Pharmacy, University of Bradford, West Yorkshire, UK.
Costall
B
B
Kelly
M E
ME
Naylor
R J
RJ
D010129:4-Aminobenzoic Acid / Q000494:pharmacology; D006916:5-Hydroxytryptophan / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D003624:Darkness; D007211:Indoles / Q000494:pharmacology; D008027:Light; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D000077526:Tropisetron; D062366:para-Aminobenzoates
D007211:Indoles; D018377:Neurotransmitter Agents; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D062366:para-Aminobenzoates; C072790:2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester; D016713:Ritanserin; D012701:Serotonin; D000077526:Tropisetron; D006916:5-Hydroxytryptophan; D010129:4-Aminobenzoic Acid