Abstract
Testing impulsive behavior in rodents is challenging and labor-intensive. We developed a new behavioral paradigm—the Variable Delay-to-Signal (VDS) test—that provides rapid and simultaneous assessment of response and decision impulsivity in rodents. Presentation of a light at variable delays signals the permission for action (nose poke) contingent with a reward. 2 blocks of 25 trials at 3 s delay flank a block of 70 trials in which light is presented with randomly selected 6 or 12 s delays. Exposure to such large delays boosts the rate of premature responses when the delay drops to 3 s in the final block, an effect that is blunted by an acute methamphetamine challenge and that correlates with the delay-discounting (DD) paradigm (choice impulsivity). Finally, as expected, treatment with the NMDA antagonist MK-801 caused a generalized response increase in all VDS blocks. The pharmacological validation, particularly with methamphetamine which has a well established dual effect on response and decision impulsivity, and the correlations between the impulsive behavior in the DD and VDS paradigms, suggests that the later is able to provide, in a single session, a multi-dimensional assessment of impulsive behavior.
Highlights
Impulsivity is defined as a tendency to act prematurely without foresight (Dalley et al, 2011)
The ability of the protocol to detect changes in impulsivity was further confirmed by an analysis of response rates, which were decreased by methamphetamine treatment and increased by acute MK-801 injections [VDS1: F(1, 16) = 4.815 p = 0.043; VDS2: F(1, 18) = 17.449 p = 0.001]
This analysis revealed that animals from all groups kept their premature response rate approximately constant across the 3 delay blocks, they increased it in the last 3 s delay [VDS1: F(3, 48) = 6.931 p = 0.011; VDS2: F(3, 54) = 28.166 p < 0.001], an effect that was present in the saline group but not in the methamphetamine group [VDS1: F(3, 48) = 8.767 p = 0.005] and was stronger in the MK-801 compared with the respective saline group [VDS2: F(3, 54) = 12.973 p < 0.001] (Figures 2B,D)
Summary
Impulsivity is defined as a tendency to act prematurely without foresight (Dalley et al, 2011). Impulsive behavior is present in rodents, both in normal conditions and in models of psychiatric disease (Adriani et al, 2003; Huskinson et al, 2012; Pattij and De Vries, 2013) It has been assessed in a number of paradigms that are well established in terms of their face, construct and predictive validity, with the go/no-go (Harrison et al, 1999), the stop-signal reaction task (SSRT; Eagle et al, 2008), the 5-choice serial reaction time task (5-csrtt; Carli et al, 1983) and the delay-discounting (DD; Evenden and Ryan, 1996) among the most used (for review see Winstanley et al, 2006; Dalley and Roiser, 2012). These paradigms have provided valuable tools to study impulsivity in rodents, they present several limitations including the extensive time commitments (spanning over 2 months in some cases), the possibility of confounding by factors like attention and reward valuation, the acquisition of repetitive behaviors (accommodation) due to the sequential performance of the paradigms and the monodimensionality of the construct assessed in each test, that limits the behavioral readouts to a single type of impulsivity
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