The effect of Δ9-tetrahydrocannabinol on the conversion of [3H]tryptophan to 5-[3H]hydroxytryptamine in the mouse brain

K. M. Johnson, W. L. Dewey

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Abstract

The effects of a 30-min pretreatment with varying doses of Δ9-tetrahydrocannabinol (Δ9-THC) on the synthesis of 5-[3H]hydroxytryptamine (5-[3H]HT) from an intravenous 10 min pulse of L-[3H]tryptophan ([3H]try) were measured in the mouse brain. They also determined the effects of Δ9-THC on several parameters believed to influence the synthesis of brain 5-HT including total and free plasma tryptophan and the high-affinity synaptosomal uptake of tryptophan. Δ9-THC was found to increase the amount of [3H]try accumulated by the brain as well as the amount of 5-[3H]HT synthesized. This effect was greater at intermediate doses than at the highest dose tested. However, Δ9-THC was determined to have no effect on the actual rate of conversion of [3H]try into 5-[3H]HT at any dose tested. Δ9-THC decreased total plasma tryptophan at low and intermediate doses, but had no effect at the highest dose tested. Synaptosomal uptake of [3H]try was unaffected by pretreatment with Δ9-THC at any dose tested. These data suggest that Δ9-THC increases the synthesis of 5-HT, not by altering the actual rate of conversion of tryptophan to 5-HT, but by altering, via an unknown mechanism, the quantity of tryptophan available for conversion to 5-HT.

Original languageEnglish (US)
Pages (from-to)140-150
Number of pages11
JournalJournal of Pharmacology and Experimental Therapeutics
Volume207
Issue number1
StatePublished - Jan 1 1978

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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