Keith L Shelton1, Katherine L Nicholson2. 1. Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, 410 North 12th Street, Room 746D, Richmond, VA, 23298-0613, USA. klshelto@vcu.edu. 2. Department of Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine, 410 North 12th Street, Room 746D, Richmond, VA, 23298-0613, USA.
Abstract
RATIONALE: Rapidly evolving e-cigarette technology developed for self-administering nicotine aerosol has the potential to be utilized to self-administer other aerosolized drugs of abuse. Rodent models which mirror characteristics of human e-cigarette use are necessary to explore the degree to which this may be a public health concern. OBJECTIVES: Our goal was to develop a highly translational model of discrete nose-only aerosol puff drug delivery to explore the reinforcing effects of fentanyl and sufentanil aerosols in rats. METHODS: Male and female Sprague-Dawley rats were trained to perform a multiple schedule FR1 lever-press, 4-s (second) nose hold operant during which the subject's orofacial areas were exposed to drug-free glycerol/propylene glycol aerosol produced by a commercial e-cigarette at a power setting of 18 watts. Each completed 4-s drug-free vehicle aerosol exposure resulted in a 3-s presentation of a 0.1-ml dipper of sweetened milk solution. After training, rats were then allowed to self-administer 4-s nose-only puffs of fentanyl (100-6000 µg/ml) or sufentanil (30-500 µg/ml) aerosol in the absence of paired milk dipper reinforcers. RESULTS: All 31 rats learned the lever-press/nose-poke multiple schedule for milk dippers alone and 25 accepted exposure to 4 s of 18 watts of drug-free vehicle aerosol when paired with milk dipper presentations. In the absence of paired milk dipper presentations, fentanyl aerosol puffs at concentrations of 1000 and 3000 µg/ml as well as 100 µg/ml puffs of sufentanil served as reinforcers compared to both air puffs and drug-free vehicle aerosol puffs. There were no significant differences between males and females in number of fentanyl or sufentanil puffs self-administered. CONCLUSIONS: Discrete nose-only puffs of two potent opioids under exposure conditions comparable to puff durations in human e-cigarette users serve as reinforcers in rats. This outcome suggests that under appropriate conditions e-cigarettes might be a potential alternative delivery mechanism for illicit opioids.
RATIONALE: Rapidly evolving e-cigarette technology developed for self-administering nicotine aerosol has the potential to be utilized to self-administer other aerosolized drugs of abuse. Rodent models which mirror characteristics of human e-cigarette use are necessary to explore the degree to which this may be a public health concern. OBJECTIVES: Our goal was to develop a highly translational model of discrete nose-only aerosol puff drug delivery to explore the reinforcing effects of fentanyl and sufentanil aerosols in rats. METHODS: Male and female Sprague-Dawley rats were trained to perform a multiple schedule FR1 lever-press, 4-s (second) nose hold operant during which the subject's orofacial areas were exposed to drug-free glycerol/propylene glycol aerosol produced by a commercial e-cigarette at a power setting of 18 watts. Each completed 4-s drug-free vehicle aerosol exposure resulted in a 3-s presentation of a 0.1-ml dipper of sweetened milk solution. After training, rats were then allowed to self-administer 4-s nose-only puffs of fentanyl (100-6000 µg/ml) or sufentanil (30-500 µg/ml) aerosol in the absence of paired milk dipper reinforcers. RESULTS: All 31 rats learned the lever-press/nose-poke multiple schedule for milk dippers alone and 25 accepted exposure to 4 s of 18 watts of drug-free vehicle aerosol when paired with milk dipper presentations. In the absence of paired milk dipper presentations, fentanyl aerosol puffs at concentrations of 1000 and 3000 µg/ml as well as 100 µg/ml puffs of sufentanil served as reinforcers compared to both air puffs and drug-free vehicle aerosol puffs. There were no significant differences between males and females in number of fentanyl or sufentanil puffs self-administered. CONCLUSIONS: Discrete nose-only puffs of two potent opioids under exposure conditions comparable to puff durations in human e-cigarette users serve as reinforcers in rats. This outcome suggests that under appropriate conditions e-cigarettes might be a potential alternative delivery mechanism for illicit opioids.
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