Authors: Eduardo R Butelman Todd J Harris Mary Jeanne Kreek
Publish Date: 2003/10/30
Volume: 172, Issue: 2, Pages: 220-224
Abstract
Salvinorin A is the active component of the hallucinogenic plant Salvia divinorum The potential mode of action of this hallucinogen was unknown until recently A recent in vitro study detected high affinity and efficacy of salvinorin A at κopioid receptors It was postulated that salvinorin A would produce discriminative stimulus effects similar to those of a high efficacy κagonist U69593 in rhesus monkeysMonkeys were previously trained to discriminate U69593 00056 or 0013 mg/kg SC from vehicle in a foodreinforced FR20 fixed ratio 20 operant conditioning procedure n=3 The ability of salvinorin A to cause generalization ≥90 U69593appropriate responding was examined in time course and cumulative doseeffect curve studiesAll subjects dosedependently emitted full U69593appropriate responding after salvinorin A 0001–0032 mg/kg SC Salvinorin Ainduced generalization started 5–15 min after injection and dissipated by 120 min The opioid antagonist quadazocine 032 mg/kg fully blocked the effects of salvinorin A The κselective antagonist GNTI 1 mg/kg 24 h pretreatment did not cause significant antagonism of the effects of salvinorin A GNTI under these conditions was only effective as an antagonist in two of three monkeys The NMDA antagonist ketamine 01–32 mg/kg was not generalized by any subject indicating that not all compounds that produce hallucinogenic or psychotomimetic effects in humans are generalized by subjects trained to discriminate U69593
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