Attenuation of delta 9-tetrahydrocannabinol-induced withdrawal-like behaviour by delta 9-tetrahydrocannabinol.
Rats chronically treated with increasing daily doses of delta 9-tetrahydrocannabinol (delta 9-THC) for up to 5 or 10 days exhibit a withdrawal-like behavioural response when challenged with clomipramine, a potent inhibitor of serotonin (5-hydroxytryptamine) reuptake, at the time when the next injection of delta 9-THC was due. To determine whether this response is indeed a withdrawal syndrome, different groups of rats were injected IV twice daily for up to 5 days with either delta 9-THC, in doses increasing from 2-6 mg/kg, or polyvinyl-pyrrolidone (PVP), the vehicle in which delta 9-THC was suspended. On day 6, an acute dose of 6 mg/kg delta 9-THC was given 30 min before IP clomipramine (15 mg/kg). The total behavioural response, which included writhing, backward kicking, jumping, head shaking, and paw tremor, was attenuated in rats chronically treated with delta 9-THC, but not in rats which received an acute dose of PVP. These results lend further evidence to our hypothesis that chronically administered delta 9-THC produces a state of physical dependence in the rat.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002997:Clomipramine / Q000494:pharmacology; D013759:Dronabinol / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000139:chemically induced / Q000503:physiopathology*
D013759:Dronabinol; D002997:Clomipramine