The gold-standard in preclinical abuse liability testing: It's all relative

Gauvin, David V.; Zimmermann, Zachary J.; Baird, Theodore J.

doi:10.1016/j.vascn.2018.08.001

Cited by 5 publications

(1 citation statement)

References 35 publications

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“…For far too long, research in behavioral pharmacology has studied the stimulus effects and reinforcing effects of drugs as separate phenomena without particular attention to their interaction. The classical model of drug reinforcement focuses principally upon the primary reinforcing effects of drugs and the secondary reinforcing effects of drug‐associated stimuli (Ator & Griffiths, 2003; Carter & Griffiths, 2009; Gauvin, Zimmermann, & Baird, 2018; 2019). However, the present findings demonstrate the critical importance of the stimulus effects of drugs and the secondary reinforcing properties they might acquire through associative pairings with reinforcing events in a user's environment.…”

Section: Discussionmentioning

confidence: 99%

Appetitive Pavlovian conditioning of the stimulus effects of nicotine enhances later nicotine self‐administration

Barrett

Flynn

Huynh

et al. 2022

J Exper Analysis Behavior

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Nicotine produces robust stimulus effects that can be conditioned to exert stimulus control over behavior through associative learning. Additionally, nicotine has weak reinforcing effects that are inconsistent with its prevalence of use and the tenacity of nicotine dependence. The present study investigated whether conditioned associations to the nicotine drug stimulus may confer additional reinforcing strength to nicotine that thereby increase its use liability, and presents a new methodological approach to investigating the interaction between the stimulus effects and reinforcing effects of drugs. Male and female Sprague–Dawley rats were divided into groups receiving intravenous infusions of either 0.03 mg/kg nicotine or 0.9% saline that were either Paired (30 s delayed) or explicitly Unpaired (4 to 6 min delayed) with sucrose deliveries over 24 daily conditioning sessions. Thereafter, recessed nosepoke response devices were installed in the chambers and infusions of their assigned drug solutions were contingently available according to a progressive ratio schedule. Rats in the Paired Nicotine condition acquired the nosepoke response, expressed active nosepoke discrimination, and self‐administered significantly more infusions than rats in any of the other groups. These results demonstrate that the interoceptive stimulus effects of nicotine can form Pavlovian associations with reinforcing events that alter its reinforcement efficacy.

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Section: Discussionmentioning

confidence: 99%

Appetitive Pavlovian conditioning of the stimulus effects of nicotine enhances later nicotine self‐administration

Barrett

Flynn

Huynh

et al. 2022

J Exper Analysis Behavior

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Toxicology and Nonclinical Safety Assessment in Pharmaceutical Discovery and Development

Reynolds

Abernathy

Baracani

et al. 2021

Burger's Medicinal Chemistry and Drug Discovery

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Nonclinical safety assessment is an essential component of drug discovery and development. Early in the drug discovery/development continuum, there are no regulatory guidelines and sponsors typically harness a range of in silico , in vitro , and short‐term in vivo toxicology screens and pilot studies to develop comparative toxicity profiles for compounds under consideration. Results from these early evaluations can be used to terminate the development of compounds with undesirable toxicity liabilities as well as to prioritize other compounds for further evaluation. As drug candidate molecules approach entry into clinical trials, regulatory expectations regarding nonclinical safety assessment become more explicit. Scientists in the pharmaceutical industry have worked with their regulatory counterparts to establish an organizational structure – the International Conference on Harmonisation (ICH) – to develop internationally accepted guidelines that specify requirements for nonclinical safety assessment activities in a phase‐specific manner. The ICH guidelines cover the need for repeat‐dose toxicology studies of increasing duration in rodents and nonrodents, safety pharmacology studies, genetic toxicity tests, immunotoxicity and immunogenicity evaluations, phototoxicity assessments, developmental and reproductive toxicity studies, and carcinogenicity assessments. In planning, conducting, and reporting these studies, the toxicologist must ensure that a fully integrated assessment of potential safety liabilities associated with the test drug is communicated to the development team so that potential safety concerns can be properly addressed.

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Reinforcing effects of fentanyl and sufentanil aerosol puffs in rats

Shelton

Nicholson

2022

Psychopharmacology

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The gold-standard in preclinical abuse liability testing: It's all relative

Cited by 5 publications

References 35 publications

Appetitive Pavlovian conditioning of the stimulus effects of nicotine enhances later nicotine self‐administration

Appetitive Pavlovian conditioning of the stimulus effects of nicotine enhances later nicotine self‐administration

Toxicology and Nonclinical Safety Assessment in Pharmaceutical Discovery and Development

Reinforcing effects of fentanyl and sufentanil aerosol puffs in rats

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