Human drug discrimination: A primer and methodological review.

Bolin, B. Levi; Alcorn, Joseph L.; Reynolds, Anna R.; Lile, Joshua A.; Rush, Craig R.

doi:10.1037/pha0000077

Cited by 25 publications

(12 citation statements)

References 108 publications

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“…Publications have fallen off considerably since 2005. This trend is remarkably similar to the trend encompassing the entire drug discrimination literature as recently reviewed [2]. The reason for this decline in the use of ethanol discrimination in understanding the behavioral pharmacology of ethanol is not readily obvious.…”

Section: Introductionsupporting

confidence: 81%

“…Indeed, the contribution to the literature can be rank ordered by rodents (89%), monkeys (7%), pigeons (2%), and humans (2%). Somewhat perplexing, given the legal and historical status of alcohol, there are far fewer human subject studies of ethanol discrimination than there are of stimulant, opiate, or cannabinoid discriminations (reviewed in Bolin et al [2] and in the section below).…”

Section: Introductionmentioning

confidence: 99%

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Cross-Species Translational Findings in the Discriminative Stimulus Effects of Ethanol

Allen

Ford

Grant

2017

Current Topics in Behavioral Neurosciences

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The progress on understanding the pharmacological basis of ethanol’s discriminative stimulus effects has been substantial, but appears to have plateaued in the past decade. Further, the cross-species translational efforts are clear in laboratory animals, but have been minimal in human subject studies. Research findings clearly demonstrate that ethanol produces a compound stimulus with primary activity through GABA and glutamate receptor systems, particularly ionotropic receptors, with additional contribution from serotonergic mechanisms. Further progress should capitalize on chemogenetic and optogenetic techniques in laboratory animals to identify the neural circuitry involved in mediating the discriminative stimulus effects of ethanol. These infrahuman studies can be guided by in vivo imaging of human brain circuitry mediating ethanol’s subjective effects. Ultimately, identifying receptors systems, as well as where they are located within brain circuitry, will transform the use of drug discrimination procedures to help identify possible treatment or prevention strategies for alcohol use disorder.

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Section: Introductionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Cross-Species Translational Findings in the Discriminative Stimulus Effects of Ethanol

Allen

Ford

Grant

2017

Current Topics in Behavioral Neurosciences

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“…Thus, Spectrum cigarettes with previously described nicotine contents of 17, 11, 5, 2, and 1 mg/g were separately tested, one per session, on discriminability from the 0.4 mg/g cigarette. Behavioral discrimination was determined by reliable detection of which cigarette was which across the separate exposures to each under blind conditions during the session (e.g., Bolin et al, 2016; Perkins et al, 2011; see 2.4.2. Specific session procedures).…”

Section: Methodsmentioning

confidence: 99%

“…As with all drugs (e.g., Bolin et al, 2016; Glennon and Young, 2011; Johanson, 1991), behavioral nicotine discrimination testing involves identifying if one dose of nicotine can be reliably detected from an identically-appearing substance containing a lower dose, or no nicotine. Nicotine discrimination testing has a long history with non-human animals (Smith and Stolerman, 2009) but not with humans (Perkins, 2009).…”

Section: Introductionmentioning

confidence: 99%

Preliminary test of cigarette nicotine discrimination threshold in non-dependent versus dependent smokers

Perkins

Kunkle

Karelitz

2017

Drug and Alcohol Dependence

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Background Despite its potential for understanding tobacco dependence, behavioral discrimination of nicotine via smoking has not been formally examined as a function of nicotine dependence level. Methods Spectrum research cigarettes were used to compare non-dependent with dependent smokers on the lowest content of nicotine they could discriminate (i.e., “threshold”). Dependent (n=21; 16 M, 5 F) or non-dependent (n=7; 4 M, 3 F) smokers were tested on ability to discriminate between cigarettes with nicotine contents of 17, 11, 5, 2, and 1 mg/g, one per session, from an “ultra-low” cigarette with 0.4 mg/g (all had 9–10 mg “tar”). All abstained from smoking overnight prior to sessions, and number of sessions was determined by the lowest nicotine content they could reliably discriminate from the ultra-low on >80% of trials (i.e., ≥5 of 6). Subjective perceptions and cigarette choice behavior were also assessed and related to discrimination behavior. Results Discrimination thresholds (and most perceptions) did not differ between dependent and non-dependent smokers, with median thresholds of 11 mg/g for both subgroups. Yet, “liking” and puff choice for threshold cigarettes were greater in dependent but not non-dependent smokers, while cigarettes with nicotine contents below threshold did not support “liking” or choice in both groups. Conclusions In sum, this preliminary study suggests threshold for discriminating nicotine via smoking may not vary by dependence level, and further study is needed to confirm that cigarettes unable to be discriminated are also not reinforcing.

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“…Considering their primarily clinical roles as antidepressants, both buspirone and fluoxetine are likely to act on circuits underlying motivation. They can differentially modulate motivated behaviors depending on its dose and context [42][43][44][45][46][47]. Motivation can highly affect motor performance.…”

Section: Serotoninergic Agents Facilitate Spinal Network That Execute Reaching and Graspingmentioning

confidence: 99%

Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury

et al. 2021

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Serotonergic agents can improve the recovery of motor ability after a spinal cord injury. Herein, we compare the effects of buspirone, a 5-HT 1A receptor partial agonist, to fluoxetine, a selective serotonin reuptake inhibitor, on forelimb motor function recovery after a C4 bilateral dorsal funiculi crush in adult female rats. After injury, single pellet reaching performance and forelimb muscle activity decreased in all rats. From 1 to 6 weeks after injury, rats were tested on these tasks with and without buspirone (1-2 mg/kg) or fluoxetine (1-5 mg/kg). Reaching and grasping success rates of buspirone-treated rats improved rapidly within 2 weeks after injury and plateaued over the next 4 weeks of testing. Electromyography (EMG) from selected muscles in the dominant forelimb showed that buspirone-treated animals used new reaching strategies to achieve success after the injury. However, forelimb performance dramatically decreased within 2 weeks of buspirone withdrawal. In contrast, fluoxetine treatment resulted in a more progressive rate of improvement in forelimb performance over 8 weeks after injury. Neither buspirone nor fluoxetine significantly improved quadrupedal locomotion on the horizontal ladder test. The improved accuracy of reaching and grasping, patterns of muscle activity, and increased excitability of spinal motor-evoked potentials after buspirone administration reflect extensive reorganization of connectivity within and between supraspinal and spinal sensory-motor netxcopy works. Thus, both serotonergic drugs, buspirone and fluoxetine, neuromodulated these networks to physiological states that enabled markedly improved forelimb function after cervical spinal cord injury.

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Human drug discrimination: A primer and methodological review.

Cited by 25 publications

References 108 publications

Cross-Species Translational Findings in the Discriminative Stimulus Effects of Ethanol

Cross-Species Translational Findings in the Discriminative Stimulus Effects of Ethanol

Preliminary test of cigarette nicotine discrimination threshold in non-dependent versus dependent smokers

Serotonergic Facilitation of Forelimb Functional Recovery in Rats with Cervical Spinal Cord Injury

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