The Discrimination of Drug Mixtures

Stolerman, I. P.

doi:10.1002/9781118023150.ch10

Cited by 4 publications

(3 citation statements)

References 83 publications

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“…It is interesting to note that in a series of investigations with drug mixtures with two-lever drug discrimination procedures, Stolerman’s laboratory showed clearer differential responding among mixtures of two drugs versus each of the elements compared to when mixtures were contrasted with saline. Contrasting each element against the mixture promotes more differential responding compared to when the mixture is not contrasted at all (see Stolerman, 2011, for a review). Positive and negative patterning procedures can only be methodologically applied to one-manipulanda go/no-go drug discrimination procedures in that each stimulus is either correlated with the primary reinforcer or not.…”

Section: Discussionmentioning

confidence: 99%

The discriminative stimulus effects of a nicotine-ethanol compound in rats: Extinction with the parts differs from the whole.

Troisi¹,

Dooley²,

Craig³

2013

Behavioral Neuroscience

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Nicotine and ethyl alcohol (EtOH) interact neurophysiologically and induce internal sensory states that contribute to their coabuse. Evaluating the combined internal sensory effects of nicotine and alcohol may be important for understanding this nexus. With rats, this investigation used an operant drug discrimination procedure to establish discriminative stimulus control with a mixture of nicotine plus EtOH (NE) at doses of nicotine (0.3 mg/kg) and EtOH (1.0 g/kg) that have previously been shown to be equally salient (Gauvin & Holloway, 1993). In Experiment (Exp) 1 the NE compound mixture continued to evoke responding despite extinction of responding with nicotine and EtOH alone. In Exp 2 the NE mixture was reliably discriminated from the nicotine and EtOH elements. Experiment 3 showed that the discriminative functions of the NE mixture emerged when the nicotine and EtOH elements were combined following their initial establishment as separate discriminative stimuli; however, nicotine evoked more control than EtOH. Extinction of responding with the NE mixture impacted rates of responding with nicotine and EtOH alone. The results of the all three studies parallel findings with exteroceptive Pavlovian literature in showing that extinction of responding with the elemental parts does not appear to impact the whole-but, extinction with the whole appears to affect its parts. The multielement discriminative function of a NE mixture appears to be a "unique cue" that differs qualitatively from nicotine or EtOH alone. Associative factors related to compound conditioning (i.e., configural learning) play an important role in mediating the discriminative functions of drug mixtures.

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Section: Discussionmentioning

confidence: 99%

The discriminative stimulus effects of a nicotine-ethanol compound in rats: Extinction with the parts differs from the whole.

Troisi¹,

Dooley²,

Craig³

2013

Behavioral Neuroscience

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“…Considering the prevalence of concurrent abuse of bath salts with MDMA or psychostimulants, a secondary aim was to assess the effects of MDPV and mephedrone in animals trained to discriminate a drug mixture. Recognizing that most psychoactive drugs have complex stimulus functions involving multiple pharmacological mechanisms of action, some researchers have utilized drug discrimination methods to evaluate the effects of drug mixtures in comparison to novel substances as a way to assess distinct components of a drug's complex stimulus functions (Stolerman 2011). Therefore, in an attempt to dissociate the discriminative stimulus effects of MDPV and mephedrone, the current study assessed these substances for stimulus generalization in rats trained to discriminate either MDMA or a drug mixture consisting of d-amphetamine and MDMA.…”

mentioning

confidence: 99%

Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture

Harvey

Baker

2015

Psychopharmacology

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Rationale Recent reports on the abuse of novel synthetic cathinone derivatives call attention to serious public health risks of these substances. In response to this concern, a growing body of preclinical research has characterized the psychopharmacology of these substances, particularly mephedrone (MEPH) or methylenedioxypyrovalerone (MDPV), noting their similarities to MDMA and cocaine. Few studies have utilized drug discrimination methodology to characterize the psychopharmacological properties of these substances. Objectives The present study employed a rodent drug discrimination assay to further characterize the stimulus effects of MEPH and MDPV in comparison to MDMA and to a drug mixture comprised of d-amphetamine and MDMA. Methods Eight male Sprague-Dawley rats were trained to discriminate 1.5 mg/kg 3, 4-methylenedioxymethamphetamine (MDMA) and eight rats were trained to discriminate a mixture of 1.5 mg/kg MDMA and 0.5 mg/kg d-amphetamine (MDMA+AMPH) from vehicle. Substitution tests were conducted with MDMA, d-amphetamine, MDPV, MEPH, and cocaine. Results Dose response curves generated with MDMA and MEPH were comparable between training groups. In contrast, AMPH, MDPV, and cocaine produced only partial substitution in animals trained to discriminate MDMA but produced full substitution in animals trained to discriminate the MDMA+AMPH mixture. Conclusions These findings indicate MDPV's effects may be more similar to those of traditional psychostimulants, whereas MEPH exerts stimulus effects more similar to those of MDMA. Additional experiments with selective DA and 5-HT receptor antagonists are required to further elucidate specific receptor mechanisms mediating the discriminative stimulus effects of MDPV and mephedrone.

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“…Thus, the higher test doses of AM5983 did not result in considerable changes in the qualitative aspects of the discriminative stimulus effects of the training drug. If the quality of the discriminative stimulus effects had changed, one would have expected a significant downward change in the percentage of drug appropriate responding (Järbe 1989; Järbe and Swedberg 1982; Overton 1988; Stolerman 2011). …”

Section: Discussionmentioning

confidence: 99%

Differentiation between low- and high-efficacy CB1 receptor agonists using a drug discrimination protocol for rats

et al. 2013

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Rationale The “subjective high” from marijuana ingestion is likely due to Δ9-tetrahydrocannabinol (THC) activating the central cannabinoid receptor type 1 (CB1R) of the endocannabinoid signaling system. THC is a weak partial agonist according to in vitro assays, yet THC mimics the behavioral effects induced by more efficacious cannabinergics. This distinction may be important for understanding similarities and differences in the dose–effect spectra produced by marijuana/THC and designer cannabimimetics (“synthetic marijuana”). Objective We evaluated if drug discrimination is able to functionally detect/differentiate between a full, high-efficacy CB1R agonist [(±)AM5983] and the low-efficacy agonist THC in vivo. Materials and methods Rats were trained to discriminate between four different doses of AM5983 (0.10 to 0.56 mg/kg), and vehicle and dose generalization curves were determined for both ligands at all four training doses of AM5983. The high-efficacy WIN55,212-2 and the lower-efficacy (R)-(+)-methanandamide were examined at some AM5983 training conditions. Antagonism tests involved rimonabant and WIN55,212-2 and AM5983. The separate (S)- and (R)-isomers of (±)AM5983 were tested at one AM5983 training dose (0.30 mg/kg). The in vitro cyclic adenosine monophosphate (cAMP) assay examined AM5983 and the known CB1R agonist CP55,940. Results Dose generalization ed50 values increased as a function of the training dose of AM5983, but more so for the partial agonists. The order of potency was (R)-isomer > (±)AM5983 > (S)-isomer and AM5983 > WIN55,212-2 ≥ THC > (R)-(+)-methanandamide. Surmountable antagonism of AM5983 and WIN55,212-2 occurred with rimonabant. The cAMP assay confirmed the cannabinergic nature of AM5983 and CP55,940. Conclusions Drug discrimination using different training doses of a high-efficacy, full CB1R agonist differentiated between low- and high-efficacy CB1R agonists.

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The Discrimination of Drug Mixtures

Cited by 4 publications

References 83 publications

The discriminative stimulus effects of a nicotine-ethanol compound in rats: Extinction with the parts differs from the whole.

The discriminative stimulus effects of a nicotine-ethanol compound in rats: Extinction with the parts differs from the whole.

Differential effects of 3,4-methylenedioxypyrovalerone (MDPV) and 4-methylmethcathinone (mephedrone) in rats trained to discriminate MDMA or a d-amphetamine + MDMA mixture

Differentiation between low- and high-efficacy CB1 receptor agonists using a drug discrimination protocol for rats

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