EFFECTS OF SYSTEMIC AND INTRA-VENTRICULAR ADMINISTRATION OF CANNABINOIDS ON SCHEDULE-CONTROLLED RESPONDING IN THE SQUIRREL-MONKEY

  • 1 January 1979
    • journal article
    • research article
    • Vol. 210  (3) , 399-404
Abstract
The effects of a number of cannabinoids in squirrel monkeys trained to respond on a chain fixed-interval fixed-ratio schedule of food presentation were determined after intraperitoneal (i.p.) and intraventricular (i.v.t.) administration. The order of potency was (.+-.)-9-nor-9.beta.-OH hexahydrocannabinol [(.+-.)-9-nor-9.beta.-OH-HHC], 11-OH-.DELTA.9-tetrahydrocannabinol [11-OH-.DELTA.9-THC], .DELTA.9-tetrahydrocannabinol (.DELTA.9-THC), cannabinol and cannabidiol. (.+-.)-9-Nor-9.alpha.-OH-HHC was inactive at doses up to 3 mg/kg i.p. and 0.1 mg/kg i.v.t. Although the order of potency was the same by both routes of administration, the i.v.t./i.p. potency ratio differed markedly. This demonstrates the importance of route of administration in assessing structure-activity relationships of cannabinoids and suggests that differences in penetration to the CNS may be an important determinant of behavioral activity. Although 11-OH-.DELTA.9-THC was more potent than the parent compound .DELTA.9-THC by both routes, the potency difference was less after i.v.t. administration. Metabolic conversion of [3H].DELTA.9-THC did not take place in squirrel monkey brain when administered i.v.t. which could account for the direct i.v.t. effects of .DELTA.9-THC. Metabolic conversion of .DELTA.9-THC in the liver is apparently not necessary for its behavioral effects.