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

Influence of Contingent and Noncontingent Drug Histories on the Development of High Levels of MDPV Self-Administration

“…Others have also reported fairly large variability in fentanyl intake in rats whose responding was maintained by intravenous or vapor fentanyl (e.g., Stevenson et al, 2020;Bakhti-Suroosh et al, 2021;McConnell et al, 2021), suggesting that fentanyl may facilitate a high-responder phenotype similar to that seen with MDPV self-administration. Taken together with recent findings suggesting that the high-responder phenotype persists when oxycodone is substituted for MDPV (Gannon et al, 2021), the current findings highlight the need to further explore interactions between this high-responder phenotype and opioid self-administration. Additionally, studies evaluating whether a history of cocaine self-administration can similarly prevent the development of this fentanyl high-responder phenotype could provide insight into the mechanism(s) that underlie the development of these high-responder phenotypes as well as their prevention by cocaine.…”

“…This upward shift in the fixed ratio (FR) 5 dose-response curve suggests that these animals are not simply more sensitive to the reinforcing effects of MDPV (i.e., not due to a leftward shift in the dose response curve), but rather that their drug-taking behavior has transitioned from well-regulated to aberrant, akin to what is observed in humans as they transition from recreational to more problematic patterns of drug-taking. In addition to high levels of drug intake, these "high-responder" rats also engage in high levels of responding during signaled periods of drug unavailability (Gannon et al, 2017(Gannon et al, , 2018b(Gannon et al, , 2021Doyle et al, 2021b), and will work harder to obtain drug infusions under PR schedules of reinforcement (Gannon et al, 2017, but see Doyle et al, 2021b, two aspects thought to be related to substance use disorders in humans (e.g., Deroche-Gamonet et al, 2004).…”

3,4-Methylenedioxypyrovalerone High-Responder Phenotype as a Tool to Evaluate Candidate Medications for Stimulant Use Disorder

“…Recently we identified a reliable and persistent high-responder phenotype that emerges in ~30% of male and female rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) and structurally-related synthetic cathinones, characterized by high levels of dysregulated drugtaking and -seeking that might be related to stimulant use disorder (Gannon et al, 2017(Gannon et al, , 2018a(Gannon et al, , 2021Doyle et al, 2021a;Abbott et al, 2022). These high-responder rats earn more infusions across a range of self-administration doses (i.e., upward shift in the dose-response curve), make more responses during signaled periods of drug unavailability, and reach greater breakpoints under progressive ratio schedules of reinforcement (Gannon et al, 2017;Doyle et al, 2021a;Abbott et al, 2022).…”

Cannabidiol Modulates the Motivational and Anxiety-Like Effects of 3,4-Methylenedioxypyrovalerone (MDPV) in Mice

“…However, due to the high variability observed in mice’s response to MDPV (around 50% reaching acquisition criteria regardless of the dose), we decided to split the group of animals into high- and low-responders for the analysis, to better elucidate CBD effects over these two groups. Previous studies have already evidenced the existence of low- and high-responder rats regarding the relative reinforcing effects of MDPV [ 21 , 51 ], albeit they used a different criterion for dividing these populations. Surprisingly, although CBD did not modify the percentage of mice reaching the acquisition criteria regardless of the drug dose, CBD modulation of MDPV self-administration was very different in the two populations for the dose 0.075 mg/kg/infusion.…”