Increased responsiveness to 5-methoxy-N,N-dimethyltryptamine in mice on a high tryptophan diet.
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Biomedical subjects
Publications and source records attributed to C A Marsden.
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Doppler shift radar was used to monitor circadian activity patterns in the rat and to study the behavioural effects of p-chloroamphetamine and d-amphetamine. Activity was classified in two ways:-(a) slow (non-locomotory) and high (locomotory) speed movements. (b) the number of starts of activity, within either the slow or high speed zones of activity during a pre-set time. p-Choloramphetamine (5 mg/kg) produced a biphasic activity response; an initial increase in continuous non-locomotory activity followed by a longer lasting increase in exploratory locomotion containing regular starts of activity. d-Amphetamine (2.5 mg/kg) produced an increase in both non-locomotory and locomotory movements but a marked reduction in starts of activity (i.e. continuous non-exploratory activity). The combination of information on the amount and pattern (starts) of activity allows a more detailed analysis of the effects of drugs on activity to be made than with existing automated methods.
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1 Control rats given L-tryptophan (100 mg/kg) showed a smaller increase of brain 5-hydroxytryptamine (5-HT) than its metabolite 5-hydroxyindoleacetic acid (5-HIAA). However, when brain 5-HT concentrations were depleted by 40-50% after treatment with the synthesis inhibitor p-chlorophenylalanine (PCPA) (150 mg/kg) L-tryptophan caused a considerable increase in 5-HT but no change in 5-HIAA. Similar results were obtained following depletion of brain 5-HT by pretreatment with p-chloroamphetamine (10 mg/kg).2 Electrical stimulation of the median raphe nucleus of control rats significantly increased 5-HIAA in the hypothalamus, hippocampus and striatum. However, stimulation of PCPA (200 mg/kg) pretreated animals did not significantly increase 5-H1AA either 24 or 72 h after administration of the drug.3 Pretreatment of rats with PCPA (200 mg/kg) increased striatal synaptosomal uptake of [(3)H]-5HT by 30% and reduced 5-HT concentration in the rest of the brain by 62%.4 PCPA (150 mg/kg) markedly reduced the acute behavioural response (-76%) to p-chloroamphetamine (10 mg/kg) although brain 5-HT was only moderately reduced (-36%). L-Tryptophan (100 mg/kg) given 15 min before p-chloroamphetamine restored both brain 5-HT and the behavioural effects of p-chloroamphetamine in PCPA pretreated rats and enhanced the behavioural response to p-chloroamphetamine in control rats.5 The results suggest that newly synthesized 5-HT is less rapidly metabolized in rats with low brain 5-HT. The possible reasons for this and the relevance of the results to the use of L-tryptophan in the treatment of depressive illness are discussed.
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