Drug discrimination is a continuous rather than a quantal process following training on a VI-TO schedule of reinforcement

Barrett, Robert J.; Caul, William F.; Huffman, Esther M.; Smith, Robert N.

doi:10.1007/bf02245196

Cited by 12 publications

(2 citation statements)

References 22 publications

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“…However, given the relatively small sample size in this study, this may be a chance Þnding, and little can be concluded regarding how these observations may contribute to our understanding of tolerance to nicotine discrimination. These Þndings would also seem to have little to contribute toward resolving whether drug discrimination is a continuous or quantal process (e.g., Barrett et al 1994).…”

Section: Discussionmentioning

confidence: 40%

Nicotine discrimination and self-administration in humans as a function of smoking status

et al. 1997

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Nicotine's discriminative stimulus effects may be critical to understanding reinforcement of tobacco smoking. It is not known whether regular nicotine exposure produces tolerance or sensitivity to these effects. In this study, male and female smokers (n = 11) and never-smokers (n = 10) were trained to discriminate 20 micrograms/kg nicotine by nasal spray from placebo (0) on day 1. On day 2, both groups were tested on generalization of this discrimination across intermittent presentations of 0, 3, 6, 12, and 20 micrograms/kg nicotine in random order. Quantitative and quantal behavioral discrimination tasks, used in previous research, were employed. On day 3, subjects were instructed to self-administer sprays from the 20 micrograms/kg nicotine versus 0 bottles in a concurrent-choice procedure. All but one subject (female smoker) learned reliably to discriminate 20 micrograms/kg nicotine from placebo (> or = 80% correct) on day 1. Nicotine-appropriate responding on day 2 was attenuated in smokers versus never-smokers at 20 micrograms/kg on the quantitative task and at 12 micrograms/kg on the quantal task, suggesting tolerance. There was no difference in responding at other doses. Smokers also showed attenuated responses on the subjective measure of "head rush", which was associated with discrimination responding in both groups. Nicotine self-administration was significantly greater in smokers versus never-smokers, who self-administered nicotine below chance levels, and was inversely related to discrimination behavior in never-smokers but unrelated in smokers. Women smokers showed less change in nicotine-appropriate responding across generalization doses, reported less confidence in discriminating training doses during acquisition on day 1, and tended to self-administer less nicotine on day 3. These results indicate that smokers may become tolerant to the discriminative stimulus effects of nicotine, perhaps promoting increased use.

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Section: Discussionmentioning

confidence: 40%

Nicotine discrimination and self-administration in humans as a function of smoking status

et al. 1997

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“…Cooperativity as indicated in these data could result from agonist-receptor interactions (Gesztelyi et al, 2012), but could also reflect physiological processes that amplify sensory signals along the pathways of their propagation (Adair, 2001). Steep dose-response functions in drug discrimination experiments frequently are observed, potentially resulting from the schedules and contingencies of reinforcement of those procedures (Barrett et al, 1994;Mathis and Emmett-Oglesby, 1990).…”

Section: Discussionmentioning

confidence: 90%

Rapid Throughput Concentration-Response Analysis of Human Taste Discrimination

Palmer¹,

Stewart²,

Talley³

2021

J Pharmacol Exp Ther

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Human taste threshold measurements often are used to infer tastant receptor functionality.However, taste thresholds can be influenced by receptor-independent variables. Examination of the full range of taste-active concentrations by taste discrimination has been hampered by logistics of testing multiple concentrations in replicate with human subjects. We developed an automated rapid throughput operant methodology for taste discrimination and applied it to concentration-response analysis of human taste. Tastant solutions (200 µl) drawn from a 96well plate and self-administered to the tongue served as discriminative stimuli for moneyreinforced responses on a touch-sensitive display. Robust concentration-response functions for "basic taste" stimuli were established, with particular focus on agonists of the TAS1R2/R3 receptor. With a training cue of 100 mM sucrose, EC50s of 56 µM, 79 µM, 310 µM, and 40 mM were obtained for rebaudioside A, sucralose, acesulfame potassium, and sucrose, respectively.Changing the sucrose training cue to 300 mM had no impact but changing to 30 mM resulted in slight leftward shifts in potencies. A signal detection method also was used to determine values of d', a probabilistic value for discriminability, which indicated that 5 mM was near the limits of detection for sucrose. With repeated testing, both EC50s and 5 mM sucrose d' values were established for each individual subject. The results showed little correspondence between threshold sensitivities and EC50 values for sucrose. We conclude that concentration-response analysis of taste discrimination provides a more reliable means of inferring receptor function than measurement of discriminability at the lowest detectable tastant concentrations. SIGNIFICANCE STATEMENTMany inferences about human tastant receptor functionality have been made from taste threshold measurements, which can be influenced by variables unrelated to receptors. We herein report a new methodology that enables rigorous concentration-response analysis of human taste discrimination, and its use toward quantitative characterization of tastant agonist This article has not been copyedited and formatted. The final version may differ from this version.

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Conditioned Taste Avoidance Drug Discrimination Procedure: Assessments and Applications

Riley

Clasen

Friar

2016

Current Topics in Behavioral Neurosciences

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In the present chapter, we summarize much of the work on the taste avoidance drug discrimination procedure, presenting the logic for its initial introduction and the extension of the procedure in the investigation of the discriminative properties of various drugs. Results from these assessments parallel those from more traditional operant and maze designs in classifying and characterizing the discriminative properties of drug. At the same time, this design reveals a procedure that is sensitive in such assessments by indexing these stimulus properties more rapidly and at lower doses than in the more traditional procedures (in some cases for drugs heretofore resistant in their detection). Importantly, much remains to be learned about the taste avoidance procedure in that the nature of such learning remains unknown and the specific parameters under which it can be established and generalized and its neurochemical and neuroanatomical bases are largely unexplored. The application of drug discrimination learning to human drug abuse continues to be an important consideration for this specific design (as well as that of drug discrimination procedures in general), and recent parallels between drug use and food intake in terms of its regulation by interoceptive stimuli suggests a possible role of the loss of stimulus control in drug escalation and addiction (with possible therapeutic implications via the modulation of these interoceptive cues).

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Drug discrimination is a continuous rather than a quantal process following training on a VI-TO schedule of reinforcement

Cited by 12 publications

References 22 publications

Nicotine discrimination and self-administration in humans as a function of smoking status

Nicotine discrimination and self-administration in humans as a function of smoking status

Rapid Throughput Concentration-Response Analysis of Human Taste Discrimination

Conditioned Taste Avoidance Drug Discrimination Procedure: Assessments and Applications

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