Acute Administration of 3,4‐Methylenedioxypyrovalerone (MDPV) Increases Motor Impulsivity in Rats

Abstract

Synthetic cathinones (SC) are one of the largest categories of emerging novel psychoactive substances, and are typically abused as ‘bath salts’ preparations. 3,4‐ methylenedioxypyrovalerone (MDPV) is a common SC frequently mentioned in both clinical case reports and calls to poison control centers, and has been implicated in increased risky behaviors. Impulsivity is a major factor in risky behaviors, and psychostimulants like cocaine may modulate baseline impulsivity through actions on dopaminergic systems. Like cocaine, the psychoactive effects of MDPV are elicited by selective and potent reuptake inhibition at catecholamine transporters, and studies from our lab have indicated that long‐term administration of MDPV increases impulsive choice in rats. The behavioral construct of impulsivity comprises multiple components, including impulsive choice and motor impulsivity. In the current study, we characterized the effects of acute MDPV on motor impulsivity using a differential reinforcement of low rate of responding (DRL 20 sec) task. Several endpoints were quantified, including number of reinforcers earned (SR), total number of premature responses (PRE), response efficiency (RE, # of reinforcers earned /total premature and reinforced responses), and perseverative responses (PRSV, # of responses following premature responses or reinforced nose pokes until the next available signaled reinforcer). Eighteen drug‐naïve, adult male Sprague‐ Dawley rats were split into three groups of six: a saline negative control (SAL), a cocaine positive control (COC), and an MDPV test group (MDPV). Animals were matched based on RE for the final five days of training (days 45–50), yielding approximately the same RE for each group (MDPV = 20.22%, COC = 19.64%, and SAL = 21.71%). Following stabilization, a satiety challenge was implemented in which animals were fed their daily allotment of food 1 hour prior to the start of their scheduled session. Satiation increased both RE and SR in all groups, while decreasing PRE and PRSV, indicating decreases in motor impulsivity. After a 5 day restabilization, each animal received an acute saline injection, followed by daily injections of either subcutaneous (SQ) saline (SAL group), 1.0 – 30.0 mg/kg intraperitoneal cocaine (COC group), or 0.1 – 3.0mg/kg SQ MDPV (MDPV group). Acute saline injections had no effect on any measure in any group, and further injections of acute saline in the SAL group had no effects on any DRL endpoints. However, escalating acute injections of both cocaine and MDPV dose dependently increased motor impulsivity. At the highest doses tested, RE was reduced to 8.36% in COC animals and to 0.81% in MDPV rats, though operant behavior was completely suppressed in 2 of the 6 MDPV animals. Moreover, the number of PRE and PRSV were increased in both COC and MDPV groups, though MDPV was more potent and effective than cocaine in this regard. Further experiments investigating the effects of long‐term MDPV administration on motor impulsivity are currently underway.Support or Funding InformationThese studies were supported in part by DA039195 and T32DA022981.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.