Drug Discrimination: Practical Considerations

doi:10.1002/9781118023150.ch3

Cited by 4 publications

References 267 publications

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Discriminative Stimulus Properties of S(−)-Nicotine: “A Drug for All Seasons”

Rosecrans

Young

2017

Current Topics in Behavioral Neurosciences

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S(-)-Nicotine is the major pharmacologically active substance in tobacco and can function as an effective discriminative stimulus in both experimental animals and humans. In this model, subjects must detect and communicate the nicotine drug state versus the non-drug state. This review describes the usefulness of the procedure to study nicotine, presents a general overview of the model, and provides some relevant methodological details for the establishment of this drug as a stimulus. Once established, the (-)-nicotine stimulus can be characterized for dose response and time course effects. Moreover, tests can be conducted to determine the similarity of effects produced by test drugs to those produced by the training dose of nicotine. Such tests have shown that the stimulus effects of nicotine are stereoselective [S(-)-nicotine >R(+)-nicotine] and that other "natural" tobacco alkaloids and (-)-nicotine metabolites can produce (-)-nicotine-like effects, but these drugs are much less potent than (-)-nicotine. Stimulus antagonism tests with mecamylamine and DHβE (dihydro-β-erythroidine) indicate that the (-)-nicotine stimulus is mediated via α4β2 nicotinic acetylcholine receptors (nAChRs) in brain; dopamine systems also are likely involved. Individuals who try to cease their use of nicotine-based products are often unsuccessful. Bupropion (Zyban) and varenicline (Chantix) may be somewhat effective as anti-smoking medications because they probably produce stimulus effects that serve as suitable substitutes for (-)-nicotine in the individual who is motivated to quit smoking. Finally, it is proposed that future drug discrimination studies should apply the model to the issue of maintenance of abstinence from (-)-nicotine-based products.

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Discriminative Stimulus Properties of S(−)-Nicotine: “A Drug for All Seasons”

Rosecrans

Young

2017

Current Topics in Behavioral Neurosciences

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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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Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and increases alcohol self-administration in rats

Besheer

Frisbee²,

Randall³

et al. 2016

Neuropharmacology

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Gabapentin, a drug used in the treatment of epileptic seizures and neuropathic pain, has shown efficacy in the treatment of alcohol dependence. Moreover, given that gabapentin is used in the general population (e.g., non-dependent individuals, social drinkers), we sought to utilize preclinical assessments to examine the effects of gabapentin on sensitivity to moderate alcohol doses and alcohol self-administration in rats with a history of moderate drinking. To this end, we assessed whether gabapentin (0, 10, 30, 120 mg/kg, IG) pretreatment alters sensitivity to experimenter- and self-administered alcohol, and whether gabapentin alone has alcohol-like discriminative stimulus effects in rats trained to discriminate a moderate alcohol dose (1 g/kg, IG) vs. water. Second, we assessed whether gabapentin (0, 10, 30, 60 mg/kg, IG) would alter alcohol self-administration in rats with a history of moderate alcohol consumption. Gabapentin pretreatment potentiated the interoceptive effects of both experimenter-administered and self-administered alcohol in discrimination-trained rats. Additionally, the highest gabapentin doses tested (30 and 120 mg/kg) were found to have partial alcohol-like discriminative stimulus effects when administered alone (e.g., without alcohol). In the self-administration trained rats, gabapentin pretreatment (60 mg/kg) resulted in an escalation in alcohol self-administration. Given the importance of interoceptive drug cues in priming and maintaining self-administration, these data define a specific behavioral mechanism (i.e., potentiation of alcohol effects) by which gabapentin may increase alcohol self-administration in non-dependent populations.

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Drug Discrimination: Practical Considerations

Cited by 4 publications

References 267 publications

Discriminative Stimulus Properties of S(−)-Nicotine: “A Drug for All Seasons”

Discriminative Stimulus Properties of S(−)-Nicotine: “A Drug for All Seasons”

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

Gabapentin potentiates sensitivity to the interoceptive effects of alcohol and increases alcohol self-administration in rats

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