Abstract
Rationale
A subset of male rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) have unusually high levels of drug intake; however, factor(s) that influence this behavior (e.g., reinforcement history and sex) are unknown.
Objectives
Characterize the reinforcing potency and effectiveness of MDPV in female rats to determine whether (1) a subset of females also develop high levels of MDPV self-administration (i.e., a high-responder phenotype) and (2) the degree to which the high-responder phenotype is influenced by various reinforcement histories (i.e., responding for cocaine or food).
Methods
Female Sprague Dawley rats initially responded for MDPV (0.032 mg/kg/infusion), cocaine (0.32 mg/kg/infusion), or food (45-mg grain pellet) under fixed ratio (FR) 1 and FR5 schedules of reinforcement. After 20 sessions, the cocaine- and food-history rats responded for MDPV for 20 additional sessions. Dose-response curves for MDPV were generated under FR5 and progressive ratio (PR) schedules of reinforcement.
Results
A subset of rats responding for MDPV developed high levels of MDPV intake. A history of responding for cocaine, but not food, inhibited the development of high levels of MDPV intake. Large individual differences were observed in the level of self-administration when MDPV was available under an FR5, but not PR, schedule of reinforcement.
Conclusions
MDPV functions as a powerful reinforcer in female rats, as has been previously reported in male rats. The substantial variability in MDPV self-administration between subjects may be related to individual differences in human drug-taking behavior.
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Acknowledgments
The authors would also like to thank Kayla Galindo, Melson Mesmin, Karen Jimenez, and Raghad Akrouk for their technical assistance in the completion of these studies.
Funding
This research was supported by the National Institutes of Health and the National Institute on Drug Abuse (R01DA039146 [GTC] and R36DA050955 [MRD]), the jointly sponsored National Institutes of Health Predoctoral Training Program in the Neurosciences (T32NS082145 [MRD]), and the Intramural Research Programs of the National Institute on Drug Abuse and the National Institute of Alcohol Abuse and Alcoholism (KCR).
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All procedures were conducted in accordance with Institutional Animal Care and Use Committee at the University of Texas Health Science Center at San Antonio and the Guide for Care and Use of Laboratory Animals (National Research Council 2011).
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Doyle, M.R., Sulima, A., Rice, K.C. et al. MDPV self-administration in female rats: influence of reinforcement history. Psychopharmacology 238, 735–744 (2021). https://doi.org/10.1007/s00213-020-05726-2
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DOI: https://doi.org/10.1007/s00213-020-05726-2