Serotonin-lesion myoclonic syndromes. II. Analysis of individual syndrome elements, locomotor activity and behavioral correlations

Abstract

This study evaluated the behavioral elements of three 5-HT-related syndromes (intraperitoneal 5-hydroxytryptophan after intracisternal 5,7-dihydroxytryptamine (DHT),p-chloroamphetamine (PCA), fenfluramine (FF), or combinations of drugs) scored from videotapes and their relationship to locomotr activity (LMA) photocell recording, regional monoamine concentration and S-1 receptor binding. Rearing was eliminated by drugs which produce the myoclonic syndrome and was the single best indicator of control treatments (saline or 5-HTP in unlesioned rats and saline in DHT-lesioned rats). Global ‘abnormality’, hunching (rigid arching of back), hindlimb abduction, forepaw myoclonus, stereotyped lateral head movements, backing, and immobility occurred significantly only on drug-treated rats. Multiple forms of myoclonus,(appendicular and truncal) and convulsions were dose-dependent drug effects. Both 5-HTP (after DHT) and PCA increased LMA significantly, but hyperactivity induced by PCA could be blocked by giving 5-HTP concomitantly. Substantial 5-HT presynaptic destruction by DHT prevented backing but not other behavioral or locomotor effects of FF and PCA. Drug combinations did not produce additive behavioral effects. Backing, immobility, and locomotor activity best differentiated between drug treatments, and could be used to correctly allocate animals to drug groups. Drug treatments also could be differentiated by reducing the number of behavioral variables into summary variables (principal components) and by discriminant analysis. Only forepaw myoclonus and total behavioral score were correlated with 5-HT concentrations (brainstem), indicating behavioral heterogeneity. Our study suggests that there is a common core ‘myoclonic-serotonergic’ syndrome (forepaw myoclonus, head weaving, hindlimb abduction, hunching) of stimulation of 5-HT receptors plus additional drug-specific elements (backing, LMA). Although brainstem receptors appear to be an important locus for some of these behaviors, S-1 receptors do not explain the behavioral supersensitivity to 5-HTP in our DHT-lesioned rats.