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MDPV “high-responder” rats also self-administer more oxycodone than their “low-responder” counterparts under a fixed ratio schedule of reinforcement

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Abstract

Rationale

Oxycodone is one of the most commonly prescribed and most frequently abused opioid analgesics, yet little is known regarding individual vulnerabilities to oxycodone abuse. The synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV) has been shown to produce a “high-responder” phenotype characterized by increased drug intake and responding during periods of signaled drug unavailability (e.g., during post-infusion timeouts) in ~ 40% of male Sprague-Dawley rats. This phenotype also transfers to other psychostimulants (e.g., cocaine and methamphetamine), but it is unknown whether this phenotype transfers to other (non-stimulant) drugs of abuse.

Objectives

The present study aimed to (1) reestablish the “high-responder” phenotype in male Sprague-Dawley rats (n = 11) that acquired self-administration of MDPV (0.032 mg/kg/inf) on a fixed ratio 1 (FR1) schedule of reinforcement and (2) compare full dose-response curves for MDPV and oxycodone self-administration under an FR5 schedule of reinforcement.

Results

MDPV was ~ 3-fold more potent at maintaining peak levels of behavior and resulted in greater overall drug intake than oxycodone. High levels of timeout responding were noted in a subset of rats that acquired MDPV self-administration (“high-responders”, n = 5), and the FR5 dose-response curve for MDPV was shifted upward for these rats relative to their “low-responder” (n = 6) counterparts. “High-responders” also self-administered more infusions of oxycodone under an FR5 schedule of reinforcement than “low-responders”; however, this was not coupled with increased levels of timeout responding.

Conclusions

The present data suggest that a subset of individuals with a history of using synthetic cathinones may be particularly vulnerable to the abuse of oxycodone.

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Funding

This research was supported by the National Institute on Drug Abuse (DA040907 and DA046215) (KSM) and the Georgia Research Alliance based in Atlanta, Georgia, by grant number GRA.VL19.I1/2 (KSM). The work of the Drug Design and Synthesis Section, MTMDB, NIDA, and NIAAA was supported by the NIH Intramural Research Programs of the National Institute on Drug Abuse (NIDA) and the National Institute of Alcohol Abuse and Alcoholism (NIAAA).

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Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Mercer University College of Pharmacy, Atlanta, GA, 30341, USA

    Brenda M. Gannon & Kevin S. Murnane

  2. Department of Pharmacology, Toxicology & Neuroscience; and the Louisiana Addiction Research Center, Louisiana State University Health Sciences Center – Shreveport, LA, 71103, Shreveport, USA

    Brenda M. Gannon & Kevin S. Murnane

  3. Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, Bethesda, MD, 20852, USA

    Kenner C. Rice

  4. Department of Psychiatry, Louisiana State University Health Sciences Center – Shreveport, Shreveport, LA, 71103, USA

    Kevin S. Murnane

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  1. Brenda M. Gannon
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Correspondence to Kevin S. Murnane.

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Gannon, B.M., Rice, K.C. & Murnane, K.S. MDPV “high-responder” rats also self-administer more oxycodone than their “low-responder” counterparts under a fixed ratio schedule of reinforcement. Psychopharmacology 238, 1183–1192 (2021). https://doi.org/10.1007/s00213-021-05764-4

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  • DOI: https://doi.org/10.1007/s00213-021-05764-4

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