Involvement of brain histamine in delta 9-tetrahydrocannabinol tolerance and withdrawal.
The involvement of brain histamine (HA) in delta 9-tetrahydrocannabinol (delta 9-THC) tolerance and dependence was studied in rats. Rats treated for 5 days with delta 9-THC (2-6 mg/kg, IV) developed tolerance to the hypothermic effects of the drug. Tolerance also developed over the 5 day period to the decrease in brain regional HA concentrations observed after an acute injection of delta 9-THC. Administration of the tricyclic antidepressant drug clomipramine hydrochloride to tolerant rats induced a withdrawal-like behavioural syndrome. Accompanying this behaviour was a fall in HA concentrations of the midbrain, cortex, medulla oblongata/pons and the cerebellum. Administration of delta 9-THC, but not of the delta 9-THC vehicle, prior to clomipramine challenge attenuated both the intensity of the withdrawal-like syndrome and the reductions in brain regional HA concentration.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001831:Body Temperature; D001921:Brain / Q000378:metabolism*; D013759:Dronabinol / Q000009:adverse effects*; D004361:Drug Tolerance; D006632:Histamine / Q000378:metabolism*; D008297:Male; D011205:Povidone / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology*
D013759:Dronabinol; D006632:Histamine; D011205:Povidone