Specificity of a rat behavioral model for serotonin receptor activation.
Pharmacological stimulation of central serotonin (5-HT) receptors causes a behavioral syndrome characterized by simultaneous side-to-side head weaving or head tremor, forepaw padding and splayed hindlimbs. This syndrome has been proposed and used as a model for 5-HT receptor activity. Questions have been raised about the possible involvement of catecholamines. This study was designed to differentiate behavioral signs contributed by 5-HT from those that might be due to catecholamines. Depletion of catecholamines by alpha-methyl-p-tyrosine, or depletion of 5-HT by either p-chlorophenylalanine or 5,7-dihydroxytryptamine, did not prevent the syndrome caused by 5-methoxy-N,N-dimethyltryptamine, a 5-HT receptor agonist. Pretreatment with methysergide, but not phenoxybenzamine or pimozide, prevented the syndrome caused by 5-methoxy-N,N-dimethyltryptamine. Conversely, 5-HT depletion prevented the syndrome caused by monoamine oxidase inhibitor and levodopa; behavioral response was restored in p-chlorophenylalanine-pretreated rats by 5-hydroxytryptophan. Methysergide prevented the syndrome caused by monoamine oxidase inhibitor and levodopa, but phenoxybenzamine or pimozide did not. Intraventricular 5-HT or dopamine also caused the behavioral syndrome after monoamine oxidase inhibition. p-Chlorophenylalanine pretreatment prevented the syndrome caused by dopamine, but did not prevent the syndrome caused by 5-HT. Our results suggest that systemic levodopa or intraventricular dopamine produces the behavioral signs through 5-HT mechanisms; endogenous catecholamine mechanisms are not involved directly in either the cause or expression of the behavioral syndrome.
D000625:Aminooxyacetic Acid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000494:pharmacology; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D008960:Models, Psychological; D008996:Monoamine Oxidase Inhibitors; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*; D012701:Serotonin / Q000494:pharmacology; D014191:Tranylcypromine / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology
D008996:Monoamine Oxidase Inhibitors; D011985:Receptors, Serotonin; D014363:Tryptamines; D000625:Aminooxyacetic Acid; D012701:Serotonin; D014191:Tranylcypromine; D007980:Levodopa; D004298:Dopamine; D008784:Methysergide