Tolerance to the effects of delta 1-tetrahydrocannabinol on the pressor responses to noradrenaline in rats.
1. The depressor response, but not the cardiac slowing response, to the acute intravenous administration of delta 1-THC (1 mg/kg) was significantly reduced in urethane anaesthetized rats, which had been treated with daily injections of delta 1-THC (2 mg/kg, i.p.) for 10 days (P less than 0.01). 2. No significant differences in either the depressor or the negative chronotropic effects of an acute intravenous injection of delta 1-THC (1 mg/kg) were observed in anaesthetized rats which had been treated with PVP (8 mg/kg per day, i.p.) for 10 days. 3. The depressor and cardiac slowing responses to an acute intravenous dose of delta 1-THC (1 mg/kg) were not significantly different between delta 1-THC- and PVP-treated animals which had been pithed. 4. The potentiating effects of delta 1-THC on the pressor responses to intravenously administered noradrenaline were significantly reduced (P less than 0.001) in urethane anaesthetized rats which had been treated with delta 1-THC, but not in anaesthetized PVP-treated animals. 5. Tolerance to the potentiating effect of delta 1-THC on the responses to noradrenaline has also been demonstrated in anaesthetized delta 1-THC-treated rats, but not in pithed delta 1-THC treated ones. 6. It is concluded that the development of tolerance to the depressor action of delta 1-THC, and its potentiating effect on the noradrenaline pressor responses requires the presence of an intact central nervous system.
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004361:Drug Tolerance; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology*; D011205:Povidone / Q000494:pharmacology; D011674:Pulse / Q000187:drug effects; D051381:Rats
D013759:Dronabinol; D011205:Povidone; D009638:Norepinephrine