Abstract
In a drug discrimination paradigm pigeons and rats were trained with an operant procedure to discriminate between the presence and absence of the effects of Δ9-THC (1.0 and 3.0 mg/kg, injected IM 90 min and I.P. 30 min before the start of the session). Once trained, various THC metabolites as well as a water-soluble derivative of THC (SP-111), were substituted for Δ9-THC to test for generalization to the training drug. Generalization to Δ9-THC occurred with the 11-hydroxy metabolites and the potency order was 11-OH-Δ9-THC >11-OH-Δ8-THC ⩾Δ9-THC. Among the other metabolites tested (8α-OH-Δ9-THC, 8α, 11-di-OH-Δ9-THC, 8β-OH-Δ9-THC, 8β, 11-di-OH-Δ9-THC), it was only 11-di-OH-Δ9-THC that completely substituted for Δ9-THC in pigeons, albeit at very high dose levels (rats were not tested with these metabolites). SP-111 generalized to Δ9-THC in both species. However, the onset of action of SP-111 was slower than that for Δ9-THC, especially in pigeons. These studies show the importance of obtaining complete dose-effect determinations over time when assessing structure-activity relationships with drug-discrimination procedures.
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Järbe, T.U.C., McMillan, D.E. Δ9-THC as a discriminative stimulus in rats and pigeons: Generalization to THC metabolites and SP-111. Psychopharmacology 71, 281–289 (1980). https://doi.org/10.1007/BF00433063
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DOI: https://doi.org/10.1007/BF00433063