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Enhancement by α-fluoromethylhistidine of the thiopental sleep-prolonging action of Δ9-tetrahydrocannabinol

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Abstract

The effect of α-fluoromethylhistidine (α-FMH), a specific inhibitor of histidine decarboxylase, on the potentiation of thiopental-induced sleep by Δ9-tetrahydrocannabinol (THC), which inhibits the histamine turnover in the brain, was examined in mice and rats. The sleeping time after injection of thiopental sodium (40 mg/kg, IV) was prolonged by THC (10 mg/kg, IP, 1 h before) to approximately twice the control value. α-FMH (50 mg/kg, IP) administered alone had no significant influence on the thiopental sleeping time. However, α-FMH given 1 or 3 h before THC treatment markedly enhanced the THC potentiation of thiopental-induced sleep. Such an enhancement by α-FMH was not observed when α-FMH was administered 15 h before THC treatment. The brain histamine level decreased by 60% during the first 4 h after α-FMH injection and remained low until 15 h after the treatment. The thiopental sleep-potentiating action of morphine, chlorpromazine and diazepam was not affected by pretreatment with α-FMH. The transient enhancing effect of α-FMH on the THC potentiation of thiopental-induced sleep suggests that the histaminergic system is one of the activating transmitter systems in the brain.

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Oishi, R., Itoh, Y., Nishibori, M. et al. Enhancement by α-fluoromethylhistidine of the thiopental sleep-prolonging action of Δ9-tetrahydrocannabinol. Psychopharmacology 95, 77–81 (1988). https://doi.org/10.1007/BF00212771

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  • DOI: https://doi.org/10.1007/BF00212771

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