MDPV self-administration in female rats: influence of reinforcement history
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ORIGINAL INVESTIGATION
MDPV self-administration in female rats: influence of reinforcement history Michelle R. Doyle 1,2 & Agnieszka Sulima 3 & Kenner C. Rice 3 & Gregory T. Collins 1,2 Received: 24 August 2020 / Accepted: 16 November 2020 # This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply 2020
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 foodhistory 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. Keywords Cocaine . MDPV . Synthetic cathinone . Self-administration . Females . Individual differences . Rat . Reinforcement history . Sex differences
Introduction Women transition from initiating substance use to seeking treatment more rapidly than men (i.e., telescoping; Griffin et al. 1989; Hernandez-Avila et al. 2004; DeVito et al. 2014), suggesting a faster progression from initial use to substance use disorder
* Gregory T. Collins [email protected] 1
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Dr - MC 7764, San Antonio, TX 78229, USA
2
South Texas Veterans Health Care System, San Antonio, TX, USA
3
Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA
(SUD). Women also use similar amounts of cocaine as men, despite initiating use later than men (Griffin et al. 1989; DeVito e
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