The synthetic cathinone 3,4-methylenedioxypyrovalerone increases impulsive action in rats

Abstract

A previous study from our laboratory has shown that the selective catecholamine reuptake inhibitor 3,4-methylenedioxypyrovalerone (MDPV) persistently alters impulsive choice as measured by delay discounting. To further understand the proimpulsive effects of MDPV, we examined its capacity to modulate a different impulsive measure - impulsive action - using a differential reinforcement of low rates of responding task with an inter-response time of 20 s. Three groups of male, Sprague-Dawley rats (n = 6) were first tested in daily sessions to understand the acute effects of cocaine (1.0-30.0 mg/kg), MDPV (0.1-3.0 mg/kg), or saline (1.0 ml/kg) on impulsive action. Both cocaine and MDPV increased impulsive action, most notably by decreasing timing error responses and response efficiency, but MDPV was more effective than cocaine. Additionally, MDPV suppressed operant responding in two of six animals at the highest dose tested. Next, the same animals received 10 postsession injections, once every other day, of either 30.0 mg/kg cocaine, 3.0 mg/kg MDPV, or 1.0 ml/kg saline based on their treatment group. An acute dose-effect redetermination was completed following the repeated administration studies, and once again MDPV and cocaine demonstrated proimpulsive effects. Interestingly, timing error responses were decreased in both MDPV and cocaine groups after an acute saline injection, potentially indicating persistent impulsive changes following the repeated administration phase of the experiment. These studies indicate that MDPV increases impulsive action acutely and that this increase may be potentiated following a series of repeated administrations.

Fig. 1

Experimental timeline for the present studies. Each line between testing phases indicates a 5-day ‘washout’ period from one testing phase to the next. Both acute dose–effect curves each started with an acute saline injection, followed by escalating doses of cocaine (1.0, 3.0, 10.0, and 30.0 mg/kg), MDPV (0.1, 0.3, 1.0, and 3.0 mg/kg), or repeated saline (1.0 ml/kg). Repeated administration was conducted with the highest doses tested in the acute phase for each drug treatment group or with 1.0 ml/kg saline for the saline treatment group. Brains were collected after a final 5-day washout. MDPV, 3,4-methylenedioxypyrovalerone.

Fig. 2

Effects of daily, acute administration of escalating doses of MDPV or cocaine or repeated saline injection, on premature responses (0–15 s IRT), timing error responses (15–20 s IRT), or reinforced responses (greater than 20 s IRT) measured when rats are drug naive (left) or following repeated administration (right) of 3.0 mg/kg MDPV, 30.0 mg/kg cocaine, or saline. Abscissa: dose of drug (mg/kg), or saline (ml/kg), based on treatment group assigned. Ordinate: specific variables expressed as a percent of the stability criteria. Group sizes indicate the number of subjects in either the cocaine or MDPV group that completed the session, at that dose.*P < 0.05 compared with the saline treatment group at each specific dose. #P < 0.05 compared with within-group acute saline administration. @P < 0.05 between MDPV and cocaine curves at each specific dose. COC, cocaine; IRT, inter-response time; MDPV, 3,4-methylenedioxypyrovalerone; SAL, saline.

Fig. 3

Effects of daily, acute administration of escalating doses of MDPV or cocaine or repeated saline injection, on the rate during the FR component, the response efficiency, or the total perseverative responses measured when rats are drug naive (left) or following repeated administration (right) of 3.0 mg/kg MDPV, 30.0 mg/kg cocaine, or saline. Abscissa: dose of drug (mg/kg), or saline (ml/kg), based on treatment group assigned. Ordinate: specific variables expressed as a percent of the stability criteria. Group sizes indicate the number of subjects in either the cocaine or MDPV group that completed the session, at that dose.*P < 0.05 compared with the saline treatment group at each specific dose. #P < 0.05 compared with within-group acute saline administration. @P < 0.05 between MDPV and cocaine curves at each specific dose. COC, cocaine; FR, fixed ratio; MDPV, 3,4-methylenedioxypyrovalerone; SAL, saline.