Interactions between impulsivity and MDPV self-administration in rats

Abstract

Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are recreational drugs of abuse often identified in 'bath salts' preparations. Humans report compulsive patterns of bath salts use, and previous work suggests that a subset of rats develop unusually high levels of MDPV self-administration. This study aims to test the hypothesis that high levels of impulsivity (e.g., inability to withhold responding for a sucrose reward) will predispose rats to high levels of MDPV self-administration relative to rats with lower levels of impulsivity. The 1-choice serial reaction time task (1-CSRTT) was used to assess impulsivity (i.e., premature responding) in 10 female and 10 male Sprague Dawley rats. Rats were then allowed to self-administer 0.032 mg/kg/inf MDPV or 0.32 mg/kg/inf cocaine, after which full dose-response curves for MDPV (0.001-0.1 mg/kg/inf) or cocaine (0.01-1 mg/kg/inf) were generated under a FR5 schedule of reinforcement. After a history of self-administering MDPV or cocaine, impulsivity was reassessed under the 1-CSRTT, prior to evaluating the acute effects of MDPV (0.032-0.32 mg/kg) or cocaine (0.1-1 mg/kg) on impulsivity. Level of impulsivity was not correlated with subsequent levels of either MDPV or cocaine self-administration, and level of drug self-administration was also not correlated with subsequent levels of impulsivity, although acute administration of MDPV and cocaine did increase premature responding. In failing to find direct relationships between either impulsivity and subsequent drug-taking behaviour, or drug-taking behaviour and subsequent assessments of impulsivity, these findings highlight the complexity inherent in the associations between impulsive behaviour and drug-taking behaviour in both animal models and humans.

Keywords: MDPV; cocaine; impulsivity; rats; self-administration; synthetic cathinones.

Figure 1.

1-CSRTT assessed prior to drug self-administration. Premature responses (top row), pellets earned (middle row), and omissions (bottom row) were recorded twice (i.e., ITI Triad Sets #1 and #2) and averaged for each drug-naive rat at ITI values of 5, 7.5, and 10 seconds. A subject’s baseline (BL) was considered to be the average of premature responses over a 5-day period after reaching stability criteria and immediately before starting ITI Triad Set #1. Rats were subdivided by sex (left column) and impulsivity (right column). Abscissa: ITI value (seconds). Ordinate: Specific variables measured during the 1-CSRTT. &P < 0.01 between female and male points. *P < 0.05 between high impulsive and low impulsive points. #P < 0.05 between mid impulsive and low impulsive points. @P < 0.05 between high impulsive and mid impulsive points.

Figure 2.

Dose-response curves for MDPV (top row) and cocaine (bottom row) self- administration obtained under the FR5 schedule of reinforcement. Rats were subdivided by sex (left column) and impulsivity (right column). Abscissa: Drug (MDPV or cocaine) dose (mg/kg/inf). Ordinate: Infusions earned per 90-minute session. Total MDPV rats: n=10 (females n=5, males n=5; HI-MDPV = 3, MI-MDPV = 5, LI-MDPV = 2). Total cocaine rats: n=9 (females n= 5, males n= 4; HI-COC = 2, MI-COC = 5, LI-COC = 2).

Figure 3.

Premature responses from the initial ITI triads arranged by drug self-administration responder group (high, middle, and low) and separated by drug (MDPV and cocaine, respectively). A subject’s baseline (BL) was considered to be the average of premature responses over a 5-day period after reaching stability criteria and immediately before starting ITI Triad Set #1. Abscissa: ITI value (seconds). Ordinate: Premature responses. #P < 0.05 between mid responder and low responder points. Total MDPV rats: n=10 (HR-MDPV = 4, MR-MDPV = 3, LR-MDPV = 3). Total cocaine rats: n=9 (HR-COC = 3, MR-COC = 3, LR-COC = 3).

Figure 4.

1-CSRTT assessed after drug self-administration. Premature responses were recorded twice (i.e., ITI Triad Sets #3 and #4) and averaged for each rat at ITI values of 5, 7.5, and 10 seconds. Rats are subdivided into sex (left column), impulsivity (middle column), drug responder (right column), and self-administered drug (MDPV, top row; cocaine, bottom row). A subject’s baseline was considered to be the average of premature responses over a 5-day period after reaching stability criteria and immediately before starting ITI Triad Set #3. Abscissa: ITI value (seconds). Ordinate: Premature responses. *P < 0.05 between mid-responder and high-responder points. Total MDPV rats: n=9 (females n=4, males n=5; HI-MDPV = 3, MI-MDPV = 4, LI-MDPV = 2; HR-MDPV = 3, MR-MDPV = 3, LR-MDPV = 3). Total cocaine rats: n=9 (females n= 5, males n= 4; HI-COC = 2, MI-COC = 5, LI-COC = 2; HR-COC = 3, MR-COC = 3, LR-COC = 3).

Figure 5.

Change scores of premature responses. A subject’s baseline (i.e. average premature responses over a 5-day period before starting 1-CSRTT triads) was calculated both before drug self-administration and after drug self-administration. Then the pre-drug baseline was subtracted from the post-drug baseline. Abscissa: MDPV or cocaine grouping. Ordinate: Difference in baseline premature responses. *P < 0.05 between cocaine females and cocaine males. Total MDPV rats: n=9 (females n=4, males n=5; HI-MDPV = 3, MI-MDPV = 4, LI-MDPV = 2; HR-MDPV = 3, MR-MDPV = 3, LR-MDPV = 3). Total cocaine rats: n=9 (females n= 5, males n= 4; HI-COC = 2, MI-COC = 5, LI-COC = 2; HR-COC = 3, MR-COC = 3, LR-COC = 3).

Figure 6.

1-CSRTT assessed 15 minutes after pretreatments with MDPV (0.032, 0.1, and 0.32 mg/kg), or cocaine (0.1, 0.32, and 1.0 mg/kg). Premature responses were recorded twice and averaged for each rat at ITI values of 5, 7.5, and 10 seconds. Rats are subdivided into impulsivity (top row) and responder (bottom row). Abscissa: ITI value (s). Ordinate: Premature responses. *P < 0.05 between mid impulsive and low impulsive points. Total MDPV rats: n=9 (females n=4, males n=5; HI-MDPV = 3, MI-MDPV = 4, LI-MDPV = 2; HR-MDPV = 3, MR-MDPV = 3, LR-MDPV = 3). Total cocaine rats: n=9 (females n= 5, males n= 4; HI-COC = 2, MI-COC = 5, LI-COC = 2; HR-COC = 3, MR-COC = 3, LR-COC = 3).