Relationship Between the Discriminative Stimulus Properties and Subjective Effects of Drugs

Schuster, C. R.; Johanson, Chris E.

doi:10.1007/978-3-642-73223-2_13

Cited by 136 publications

(107 citation statements)

References 19 publications

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“…However, it is unclear if the responses evoked by these stimuli are truly the result of classical conditioning mechanisms, or whether they result from other learning or memory processes (eg, implicit or explicit memories or associations, or discriminative stimuli signaling drug availability (Schuster and Johanson, 1988)). To study the process of Pavlovian acquisition of these responses, we previously developed a novel drug conditioning paradigm (Mayo et al, 2013) to study the acquisition of de novo drug cues in healthy adults.…”

Section: Introductionmentioning

confidence: 99%

Acquisition of Responses to a Methamphetamine-Associated Cue in Healthy Humans: Self-Report, Behavioral, and Psychophysiological Measures

Mayo

Wit

2015

Neuropsychopharmacol

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Drug-associated cues elicit conditioned responses in human drug users, and are thought to facilitate a drug-seeking behavior. Yet, little is known about how these associations are acquired, or about the specificity of the conditioned response modalities. In this study, healthy, nondependent volunteers (N ¼ 90) completed a conditioning paradigm in which they received a moderate dose of methamphetamine paired with one stimulus and placebo with another stimulus, each on two separate occasions. Their responses to these cues were measured with a behavioral preference, self-reported 'liking', emotional reactivity, and attentional bias measures, both before and after the conditioning. Following the conditioning procedure, subjects exhibited a behavioral preference, positive emotional reactivity, and attentional bias toward the methamphetamine-associated cue, compared with the placebo stimulus. In addition, subjects who reported greater positive subjective drug effects during the conditioning displayed a more robust conditioning. This work demonstrates that healthy nondependent volunteers readily acquire conditioned responses to neutral stimuli paired with a drug. The procedure has significant value to study individual variation in acquisition of conditioned responses as a possible risk factor for drug taking, and to study the neural basis of conditioned drug responses.

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Section: Introductionmentioning

confidence: 99%

Acquisition of Responses to a Methamphetamine-Associated Cue in Healthy Humans: Self-Report, Behavioral, and Psychophysiological Measures

Mayo

Wit

2015

Neuropsychopharmacol

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“…Although exceptions have been noted [Ator et al, 1993;Ator, 1994], there is a strong correlation between discriminative stimuli in non-verbal species and subjective effects reported by humans [Schuster and Johanson 1988;Balster 1990;Sanger et al 1994;Brauer et al 1997]. Although drug-induced stimulus control has been established in humans [for reviews see Kamien et al, 1993;Brauer et al, 1997;Dykstra et al, 1997] and in a number of animal species, the majority of studies have employed the rat [Stolerman and Kamien, 2004].…”

Section: Introductionmentioning

confidence: 99%

The stimulus properties of LSD in C57BL/6 mice

Winter¹,

Kieres²,

Zimmerman³

et al. 2005

Pharmacology Biochemistry and Behavior

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Rationale-Drug-induced stimulus control has proven to be a powerful tool for the assessment of a wide range of psychoactive drugs. Though a variety of species have been employed, the majority of studies have been in the rat. However, with the development of techniques which permit the genetic modification of mice, the latter species has taken on new importance. Lysergic acid diethylamide [LSD], the prototypic indoleamine hallucinogen, has not previously been trained as a discriminative stimulus in mice.Objective-To demonstrate the feasibility of LSD-induced stimulus control in the mouse and to provide a preliminary characterization of the stimulus properties of LSD in that species.Methods-Male C57BL/6 mice were trained using a left or right nose-poke operant on a fixed-ratio 10, water reinforced task following the injection of lysergic acid diethylamide [LSD, 0.17 or 0.30 mg/kg, SC; 15 min pretreatment] or vehicle.Results-Stimulus control was established in 6 of 16 mice at a dose of LSD of 0.17 mg/kg after 39 sessions. An increase in dose to 0.30 mg/kg for the remaining mice resulted in stimulus control in an additional 5 subjects. In the low dose group, subsequent experiments demonstrated an orderly dose-effect relationship for LSD and a rapid offset of drug action with an absence of LSD effects 60 min after injection. When LSD [0.17 mg/kg] was administered in combination with the selective 5-HT 2A antagonist, M100907, LSD-appropriate responding was significantly but incompletely reduced to approximately 50%; concurrently, response rates declined significantly. In mice trained with a dose of LSD of 0.30 mg/kg, full generalization to the phenethylamine hallucinogen, [-]-2,5-dimethoxy-4-methylamphetamine [DOM] was observed.Conclusions-The present data demonstrate the feasibility of LSD-induced stimulus control in the mouse. The general features of stimulus control by LSD in the mouse closely resemble those observed in the rat but the present data suggest that there may be significant differences as well.

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“…Drug discrimination procedures are a well-established animal model for classifying novel compounds with putative psychoactive actions because they allow for a comparison between novel substances and known psychoactive drugs (Schuster and Johanson 1988;Balster 1991). Salvinorin A has not yet been evaluated extensively in drug discrimination procedures, although a few studies have tested salvinorin A in rhesus monkeys (Butelman et al 2004) or rats (Willmore-Fordham et al 2007) trained to discriminate the kappa agonist U69,593 or monkeys trained to discriminate the serotonergic hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM; Li et al 2008).…”

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confidence: 99%

Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats

et al. 2009

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Background and rationale Research interests regarding the psychopharmacology of salvinorin A have been motivated by the recreational use and widespread media focus on the hallucinogenic plant, Salvia divinorum. Additionally, kappa opioid (KOP) receptor ligands may have therapeutic potential in the treatment of some neuropsychiatric conditions, including drug dependence and mood disorders. Salvinorin A is a selective KOP agonist, but only a few studies have explored the discriminative stimulus effects of this compound. Objective This study compared the discriminative stimulus effects of salvinorin A and two synthetic derivatives of salvinorin B to the KOP agonists, U69,593 and U50,488. Materials and methods Sixteen male Sprague-Dawley rats trained to discriminate U69,593 (0.13 mg/kg, s.c., N=8) or U50,488 (3.0 mg/kg, i.p., N=8) under a fixed-ratio 20 schedule of food reinforcement were administered substitution tests with salvinorin A (0.125-3.0 mg/kg, i.p.). The animals trained to discriminate U69,593 were also administered substitution tests with salvinorin B ethoxymethyl ether (0.005-0.10 mg/kg, i.p.) and salvinorin B methoxymethyl ether (0.03-0.10 mg/kg, i.p.). Another eight rats were trained to discriminate 2.0 mg/kg salvinorin A and tested with U69,593 (0.04-0.32 mg/kg) and U50,488 (0.4-3.2 mg/kg). Results Salvinorin A and both synthetic derivatives of salvinorin B substituted completely for U69,593. Additionally, cross-generalization was observed between salvinorin A and both KOP agonists.Conclusion These findings support previous reports indicating that the discriminative stimulus effects of salvinorin A are mediated by kappa receptors. Future studies may assist in the development and screening of salvinorin A analogs for potential pharmacotherapy.

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Relationship Between the Discriminative Stimulus Properties and Subjective Effects of Drugs

Cited by 136 publications

References 19 publications

Acquisition of Responses to a Methamphetamine-Associated Cue in Healthy Humans: Self-Report, Behavioral, and Psychophysiological Measures

Acquisition of Responses to a Methamphetamine-Associated Cue in Healthy Humans: Self-Report, Behavioral, and Psychophysiological Measures

The stimulus properties of LSD in C57BL/6 mice

Comparison of the discriminative stimulus effects of salvinorin A and its derivatives to U69,593 and U50,488 in rats

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