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Circadian variation in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine and p-chloroamphetamine in the mouse

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Abstract

Circadian fluctuations were measured in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine (5-MeODMT) and p-chloroamphetamine (PCA) in male BK. TO mice. The effects of depleting brain 5-hydroxytryptamine (5-HT) with p-chlorophenylalanine (PCPA) on the 5-MeODMT in the mouse were also studied. Changes in brain 5-HT and 5-hydroxyindoleacetic (5-HIAA) were concomitantly determined. PCPA (400 mg/kg IP twice on consecutive days) significantly increased the number of head twitches induced by 5-MeODMT (5 mg/kg IV) on days 3 and 5 after the initial injection of PCPA when 5-HT and 5-HIAA were also significantly reduced. On day 12, there was no significant difference in the number of head twitches between mice administered PCPA and those given saline, and 5-HT and 5-HIAA levels were nearly back to normal. PCPA, using the same dose schedule, significantly reduced the number of head twitches induced by PCA when PCA was administered 24h after the second injection of PCPA (day 3). Mice maintained on a 12-h light-dark cycle showed a maximum response to the direct 5-HT receptor agonist 5-MeODMT (5 mg/kg IV) towards the end of the dark period, when the 5-HT level was at its lowest. p-Chloroamphetamine, which causes release of 5-HT from pre-synaptic neurones, produced a peak head twitch response in the middle of the light period when 5-HT and 5-HIAA levels were maximal, while the response towards the end of the dark period was significantly less than that at other tines tested. It is concluded that 5-HT receptor response shows a circadian rhythm related to both pre-synaptic availability of 5-HT and post-synaptic receptor sensitivity.

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Singleton, C., Marsden, C.A. Circadian variation in the head twitch response produced by 5-methoxy-N1,N1-dimethyltryptamine and p-chloroamphetamine in the mouse. Psychopharmacology 74, 173–176 (1981). https://doi.org/10.1007/BF00432688

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