Katharine H Nelson1, Briana J Hempel2, Matthew M Clasen2, Kenner C Rice3, Anthony L Riley4. 1. Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, D.C. 20016, USA. Electronic address: kn9165a@student.american.edu. 2. Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, D.C. 20016, USA. 3. Drug Design and Synthesis Section, National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD 20892, USA. 4. Psychopharmacology Laboratory, Center for Behavioral Neuroscience, American University, 4400 Massachusetts Ave, NW, Washington, D.C. 20016, USA. Electronic address: alriley@american.edu.
Abstract
BACKGROUND: α-Pyrrolidinopentiophenone (α-PVP) has been reported to be rewarding in a variety of pre-clinical models. Given that a number of drugs of abuse have both rewarding and aversive effects, the balance of which influences addiction potential, the present study examined the aversive properties of α-PVP by assessing its ability to induce taste avoidance. This assessment was made in a combined taste avoidance/place conditioning design that also allowed an evaluation of the relationship between α-PVP's aversive and rewarding effects. METHODS: Male Sprague-Dawley rats were exposed to a novel saccharin solution, injected with one of four doses of α-PVP (0, 0.3, 1.0 and 3.0mg/kg) (IP) and placed on one side of a place conditioning apparatus. The next day, they were injected with vehicle, given access to water and placed on the other side. Following four conditioning cycles, saccharin avoidance and place preferences were then assessed. The effects of α-PVP on body temperature were also examined. RESULTS: α-PVP induced dose-dependent taste avoidance as well as significant increases in time spent on the drug-paired side (although this effect was not dependent on dose). α-PVP also induced dose- and time-dependent hyperthermia. CONCLUSIONS: α-PVP induced significant taste avoidance whose strength relative to the psychostimulants methylenedioxypyrovalerone (MDPV) and cocaine paralleled their relative binding to the dopamine transporter. Similar to other drugs of abuse, α-PVP has both aversive and rewarding effects. It will be important to assess how various experiential and subject variables impact these effects and their balance to predict abuse liability.
BACKGROUND: α-Pyrrolidinopentiophenone (α-PVP) has been reported to be rewarding in a variety of pre-clinical models. Given that a number of drugs of abuse have both rewarding and aversive effects, the balance of which influences addiction potential, the present study examined the aversive properties of α-PVP by assessing its ability to induce taste avoidance. This assessment was made in a combined taste avoidance/place conditioning design that also allowed an evaluation of the relationship between α-PVP's aversive and rewarding effects. METHODS: Male Sprague-Dawley rats were exposed to a novel saccharin solution, injected with one of four doses of α-PVP (0, 0.3, 1.0 and 3.0mg/kg) (IP) and placed on one side of a place conditioning apparatus. The next day, they were injected with vehicle, given access to water and placed on the other side. Following four conditioning cycles, saccharin avoidance and place preferences were then assessed. The effects of α-PVP on body temperature were also examined. RESULTS: α-PVP induced dose-dependent taste avoidance as well as significant increases in time spent on the drug-paired side (although this effect was not dependent on dose). α-PVP also induced dose- and time-dependent hyperthermia. CONCLUSIONS: α-PVP induced significant taste avoidance whose strength relative to the psychostimulants methylenedioxypyrovalerone (MDPV) and cocaine paralleled their relative binding to the dopamine transporter. Similar to other drugs of abuse, α-PVP has both aversive and rewarding effects. It will be important to assess how various experiential and subject variables impact these effects and their balance to predict abuse liability.
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