delta 9-Tetrahydrocannabinol decreases turnover of brain histamine.
Histamine (HA) is a neurotransmitter present in the brain. As there is little information on the effect of delta 9-tetrahydrocannabinol (delta 9-THC) on brain histaminergic activity, the possible delta 9-THC-induced changes in brain HA turnover were studied in rats and mice. Whereas various doses of delta 9-THC had no influence on the brain HA levels in these species, high doses of delta 9-THC reduced the content of tele-methylhistamine (t-MH), a predominant HA metabolite in the brain, in mice. A moderate dose of delta 9-THC was effective in decreasing the brain t-MH content in the rats. Pargyline (65 mg/kg i.p.) caused a 101 ng/g accumulation of t-MH in mice and an 80 ng/g accumulation of t-MH in rats 105 min after the injection. delta 9-THC significantly suppressed the pargyline-induced t-MH accumulation at 50 mg/kg in mice whereas only 2 mg/kg of this compound was effective in rats, when administered i.v. 15 min after pargyline treatment. delta 9-THC (50 mg/kg i.v.) delayed the depletion of neuronal HA in the mouse brain, as induced by treatment with a specific histidine decarboxylase inhibitor alpha-fluoromethylhistidine (50 mg/kg i.p.). delta 9-THC (30 and 100 microM) significantly inhibited the K+-induced release of endogenous HA from guinea-pig hypothalamic slices. These results suggest that delta 9-THC decreases HA turnover in the brain.
Oishi
R
R
Itoh
Y
Y
Nishibori
M
M
Saeki
K
K
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D013759:Dronabinol / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism*; D006636:Histamine Release / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000378:metabolism; D008762:Methylhistidines / Q000494:pharmacology; D051379:Mice; D010293:Pargyline / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D008761:Methylhistamines; D008762:Methylhistidines; C028309:alpha-fluoromethylhistidine; D013759:Dronabinol; D006632:Histamine; D010293:Pargyline; C020404:tele-methylhistamine