Mehrak Javadi-Paydar1, Eric L Harvey1, Yanabel Grant1, Sophia A Vandewater1, Kevin M Creehan1, Jacques D Nguyen1, Tobin J Dickerson2, Michael A Taffe3. 1. Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA. 2. Department of Chemistry, The Scripps Research Institute, La Jolla, CA, USA. 3. Department of Neuroscience, The Scripps Research Institute, 10550 North Torrey Pines Road, SP30-2400, La Jolla, CA, 92037, USA. mtaffe@scripps.edu.
Abstract
RATIONALE: The synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone. OBJECTIVES: The binge-like acquisition pattern is novel for rat IVSA; thus, the present study sought to determine if this effect generalizes to IVSA of α-PVP in female rats. METHODS: Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers containing an activity wheel. Groups were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move. RESULTS: Approximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution. CONCLUSION: This confirms the high reinforcer effectiveness of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.
RATIONALE: The synthetic cathinone α-pyrrolidinopentiophenone (α-PVP) has been associated with bizarre public behavior in users. Association of such behavior with extended binges of drug use motivates additional investigation, particularly since a prior study found that half of male rats experience a binge of exceptionally high intake, followed by sustained lower levels of self-administration during the acquisition of intravenous self-administration (IVSA) of a related drug, 3,4-methylenedioxypyrovalerone. OBJECTIVES: The binge-like acquisition pattern is novel for rat IVSA; thus, the present study sought to determine if this effect generalizes to IVSA of α-PVP in female rats. METHODS: Female Wistar rats were trained in IVSA of α-PVP (0.05 mg/kg/inf) in experimental chambers containing an activity wheel. Groups were trained with the wheels fixed (No-Wheel group), fixed for the initial 5 days of acquisition or free to move throughout acquisition (Wheel group). The groups were next subjected to a wheel access switch and then all animals to dose-substitution (0.0125-0.3 mg/kg/inf) with the wheels alternately fixed and free to move. RESULTS: Approximately half of the rats initiated their IVSA pattern with a binge day of exceptionally high levels of drug intake, independent of wheel access condition. Wheel activity was much lower in the No-Wheel group in the wheel switch post-acquisition. Dose-effect curves were similar for wheel access training groups, for binge/no binge phenotypic subgroups and were not altered with wheel access during the dose-substitution. CONCLUSION: This confirms the high reinforcer effectiveness of α-PVP in female rats and the accompanying devaluation of wheel activity as a naturalistic reward.
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