Drug‐induced discrimination: A description of the paradigm and a review of its specific application to the study of hallucinogenic agents

Glennon, Richard A.; Rosecrans, John A.; Young, Richard

doi:10.1002/med.2610030305

Cited by 85 publications

(41 citation statements)

References 68 publications

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“…This popular assay has proven useful given that the discriminative stimulus effects of drugs in animals parallel the subjective drug effects in humans (Brauer et al 1997;Goudie and Leathley 1993). Moreover, it has been shown to be a stable, specific, and sensitive measure of dose-related drug effects (Glennon et al 1983).…”

Section: Introductionmentioning

confidence: 99%

Reinforcement schedule effects in rats trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or cocaine

Kueh

Baker

2006

Psychopharmacology

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Rationale Relatively few studies have compared the discriminative stimulus effects of 3,4-methylenedioxymethamphetamine (MDMA) and cocaine, and findings from different laboratories are somewhat inconsistent. One possible reason for discrepant results may be the use of different reinforcement schedules during discrimination training. Objective The present study compared fixed ratio (FR) 20 and variable interval (VI) 15-s reinforcement schedules to determine their influence on discrimination acquisition, response rates, frequency of reinforcements, and stimulus generalization in rats trained to discriminate cocaine or MDMA. Materials and methods Thirty-two male Sprague-Dawley rats were trained to discriminate cocaine (10 mg/kg; n=16) or MDMA (1.5 mg/kg; n=16) from saline under either a FR 20 or a VI 15-s schedule of food reinforcement. Stimulus generalization tests were conducted with a range of doses of cocaine, MDMA, d-amphetamine, and lysergic acid diethylamide in all four training groups. Results The FR 20 schedule facilitated more rapid discrimination acquisition compared to the VI 15-s schedule and established differential response rates and frequency of reinforcement under drug and vehicle conditions. However, reinforcement schedule had little influence on stimulus generalization between MDMA and cocaine. Cocaine produced partial substitution for MDMA in both training groups (FR 20, 51%; 58%). Likewise, MDMA produced only partial substitution for cocaine in both training groups (FR 20, 40%; 72%). Conclusions The present findings suggest that the number of sessions required to establish discriminative stimulus control varies with different reinforcement schedules. Nevertheless, training schedules alone do not appear to have significant effects on stimulus generalization between MDMA and cocaine.

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Section: Introductionmentioning

confidence: 99%

Reinforcement schedule effects in rats trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or cocaine

Kueh

Baker

2006

Psychopharmacology

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“…In addition, behavioral studies (Glennon et al 1983), electrophysiological studies (Rasmussen and Aghajanian 1988) and radioligand binding studies (Shannon et al J984;Lyon et al 1987) indicate that these hallucinogenic drugs are 5-HTz receptor agonists. In rat drug discrimination studies it was shown that rats trained to discriminate DOM (4-methyl-2,5-dimethoxyphenylisopropylamine) recognized and responded in a dosedependent manner to such agents as d-LSD, DOI and DOB (for review see Glennon et al 1984a). This stimulus generalization was potently blocked by the 5-HT2 receptor antagonists ketanserin and pirenperone (Glennon et al 1983).…”

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confidence: 99%

Hallucinogenic drug interactions at human brain 5-HT2 receptors: implications for treating LSD-induced hallucinogenesis

et al. 1989

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It has been shown that the hallucinogenic potencies of LSD, the phenylisopropylamines, such as DOB (4-bromo-2,5-dimethoxyphenylisopropylamine) and DOI (4-iodo-2,5-dimethoxyphenylisopropylamine), and the indolealkylamines, such as DMT (dimethyltryptamine) and 5-OMe-DMT (5-methoxy-dimethyltryptamine), strongly correlate with their in vitro 5-HT2 receptor binding affinities in rat cortical homogenates. In order to ascertain if this correlation applies to human 5-HT2 receptors as well, we examined the affinities of 13 psychoactive compounds at 3H-ketanserin-labelled 5-HT2 receptors in human cortical samples. Both radioligand binding and autoradiographical procedures were used. As in rat brain, d-LSD was the most potent displacer of 3H-ketanserin specific binding with a Ki of 0.9 nM. The phenylisopropylamine DOI also displayed high affinity (Ki of 6 nM). Stereospecific interactions were found with DOB; (-) DOB had a Ki of 17 nM while (+) DOB had a Ki of 55 nM. The behaviorally active compound DOM (4-methyl-2,5-phenylisopropylamine) had an affinity of 162 nM while its behaviorally less active congener iso-DOM had an affinity of 6299 nM. The indolealkylamines 5-OMe-DMT and DMT competed with moderate affinities (207 and 462 nM, respectively). In general, Hill coefficients were significantly less than unity which is consistent with an agonist interaction with 5-HT2 receptors. MDMA, a substituted amphetamine analog was inactive with a Ki of greater than 10 microM. A strong correlation was found for the hallucinogen affinities and human hallucinogenic potencies (r = 0.97). Also, human and rat brain 5-HT2 receptor affinities were strongly correlated (r = 0.99). These results strongly support the hypothesis that the hallucinogenic effects of these drugs in humans are mediated in whole or in part via 5-HT2 receptors. Furthermore, these studies imply that treatment with 5-HT2 receptor antagonists may be effective in reversing the hallucinogenic effects caused by the ingestion of LSD and LSD-like drugs.

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“…Several studies have established stimulus control with DOM in rats and examined the structure-activity relationships for various drugs acting on serotonergic (5-HT) systems (for reviews, see Glennon et al, 1983b;Glennon, 1988;Winter et al, 1999). DOM exerts pharmacologically selective stimulus effects that appear to be due to actions at a specific type of 5-HT receptor, and it is possible that this discrimination procedure is related to the hallucinogenic effects of drugs (Glennon, 1988).…”

mentioning

confidence: 99%

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane in Rhesus Monkeys

Rice

2007

J Pharmacol Exp Ther

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Discriminative stimulus effects of 1-(2,5-dimethoxy-4-methylphenyl)-2-aminopropane (DOM) and related drugs have been studied extensively in rodents, although the generality of those findings across species is not known. The goals of this study were to see whether monkeys could discriminate DOM and to characterize the DOM discriminative stimulus by studying a variety of drugs, including those with hallucinogenic activity in humans. Four rhesus monkeys discriminated between 0.32 mg/kg s.c. DOM and vehicle after an average of 116 (range ϭ 85-166) sessions while responding under a fixed ratio 5 schedule of stimulus shock termination.

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Drug‐induced discrimination: A description of the paradigm and a review of its specific application to the study of hallucinogenic agents

Cited by 85 publications

References 68 publications

Reinforcement schedule effects in rats trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or cocaine

Reinforcement schedule effects in rats trained to discriminate 3,4-methylenedioxymethamphetamine (MDMA) or cocaine

Hallucinogenic drug interactions at human brain 5-HT2 receptors: implications for treating LSD-induced hallucinogenesis

Discriminative Stimulus Effects of 1-(2,5-Dimethoxy-4-methylphenyl)-2-aminopropane in Rhesus Monkeys

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