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Discriminative stimulus properties of lysergic acid diethylamide in the monkey.

E. B. Nielsen

Journal of Pharmacology and Experimental Therapeutics July 1, 1985 DOI: 10.1016/s0022-3565(25)23328-6 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Animal drug discrimination study Peer reviewed
Sample size 4
Population Four vervet monkeys (Cercopithecus aethiops)
Interventions Lysergic acid diethylamide (LSD) lisuride 5-methoxy-N N-dimethyltryptamine mescaline d-amphetamine apomorphine ketanserin pirenperone clozapine haloperidol pizotifen
Dose LSD training dose 0.06 mg/kg; LSD ED50 0.011 mg/kg; lisuride ED50 0.0098 mg/kg; 5-methoxy-N,N-dimethyltryptamine ED50 0.45 mg/kg; mescaline 1-40 mg/kg; d-amphetamine 0.1-0.625 mg/kg; apomorphine 0.1-0.5 mg/kg; ketanserin 1-10 mg/kg; pirenperone 0.025, 0.05, and 0.1 mg/kg; clozapine 1 and 2 mg/kg; haloperidol 0.1 mg/kg; pizotifen 0.6-1.8 mg/kg
Topics LSD
Key points Lisuride, which does not readily cause hallucinations in humans, fully substituted for LSD in monkeys, while mescaline did not, leading the authors to suggest that the LSD discriminative cue may not reflect LSD's hallucinogenic properties and may depend on poorly characterized receptors, possibly serotonergic.

Abstract

Four monkeys (Cercopithecus aethiops) were trained to discriminate 0.06 mg/kg of lysergic acid diethylamide (LSD) from saline in a two-key task in which correct responding was reinforced with food under a fixed ratio 32 schedule. The ED50 of LSD was 0.011 mg/kg. The nonhallucinogenic ergot, lisuride, and the hallucinogen, 5-methoxy-N,N-dimethyltryptamine, substituted completely for LSD (ED50 values were 0.0098 and 0.45 mg/kg, respectively). Mescaline (1-40 mg/kg), d-amphetamine (0.1-0.625 mg/kg) and apomorphine (0.1-0.5 mg/kg) did not substitute for LSD. In antagonism testing with ketanserin (1-10 mg/kg) or pirenperone (0.025 and 0.05 mg/kg), only the highest dose of pirenperone attenuated the LSD stimulus effect (to 55%). A 0.1-mg/kg dose of pirenperone produced nonresponding in three of four animals. The LSD cue was unaffected by clozapine (1 and 2 mg/kg), haloperidol (0.1 mg/kg) and pizotifen (0.6-1.8 mg/kg). The fact that lisuride does not readily cause hallucinations in humans, but yet substituted for LSD in primates, indicates that the LSD cue may not reflect the hallucinogenic properties of LSD. It is suggested that the LSD stimulus effect may depend on receptors (e.g., serotonergic) that, at the moment, are only poorly characterized.