Using a dependent schedule to measure risky choice in male rats: Effects of d-amphetamine, methylphenidate, and methamphetamine

Abstract

Risky choice is the tendency to choose a large, uncertain reward over a small, certain reward, and is typically measured with probability discounting, in which the probability of obtaining the large reinforcer decreases across blocks of trials. One caveat to traditional procedures is that independent schedules are used, in which subjects can show exclusive preference for one alternative relative to the other. For example, some rats show exclusive preference for the small, certain reinforcer as soon as delivery of the large reinforcer becomes probabilistic. Therefore, determining if a drug increases risk aversion (i.e., decreases responding for the probabilistic alternative) is difficult (due to floor effects). The overall goal of this experiment was to use a concurrent-chains procedure that incorporated a dependent schedule during the initial link, thus preventing animals from showing exclusive preference for one alternative relative to the other. To determine how pharmacological manipulations alter performance in this task, male Sprague-Dawley rats (n = 8) received injections of amphetamine (0, 0.25, 0.5, 1.0 mg/kg), methylphenidate (0, 0.3, 1.0, 3.0 mg/kg), and methamphetamine (0, 0.5, 1.0, 2.0 mg/kg). Amphetamine (0.25 mg/kg) and methylphenidate (3.0 mg/kg) selectively increased risky choice, whereas higher doses of amphetamine (0.5 and 1.0 kg/mg) and each dose of methamphetamine impaired stimulus control (i.e., flattened the discounting function). These results show that dependent schedules can be used to measure risk-taking behavior and that psychostimulants promote suboptimal choice when this schedule is used. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Figure 1.

Schematic illustrating two trials in the concurrent-chains procedure for one rat. For this particular rat, the left lever is associated with the large, uncertain reinforcer, and the right lever is associated with the small, certain reinforcer. During the initial link, the lever that allows the rat to advance to the terminal link is determined by the program (this is the dependent schedule). In trial 1, responses on the left lever are recorded during the initial link but have no programmed consequence. In this case, the rat has to complete the response requirement (FR 5) on the right lever to end the initial link. After a 2-s delay, the terminal link begins. Responses on the left lever are recorded but have no programmed consequence. Completing the response requirement (FR 3) on the right lever results in delivery of one sucrose-based pellet. In trial 2, responses on the right lever during the initial link are recorded but have no programmed consequences. The rat has to respond on the left lever to advance to the terminal link. During the terminal link, responses on the right lever are recorded but have no programmed consequences. Completing the response requirement on the left lever results in probabilistic delivery of four sucrose-based pellets. For each rat, the active lever (i.e., the lever that ends the initial link and the lever that leads to reinforcement) is pseudo-randomized across trials, such that each lever leads to reinforcement on an equal number of trials (5 trials each per block; 25 total trials across the session). Abbreviations: HL = house light; ITI = inter-trial interval; LL = left lever; LSL = left stimulus light; OA = odds against (note: odds against = [1/probability]-1); RR = right lever; RSL = right stimulus light.

Figure 1.

Schematic illustrating two trials in the concurrent-chains procedure for one rat. For this particular rat, the left lever is associated with the large, uncertain reinforcer, and the right lever is associated with the small, certain reinforcer. During the initial link, the lever that allows the rat to advance to the terminal link is determined by the program (this is the dependent schedule). In trial 1, responses on the left lever are recorded during the initial link but have no programmed consequence. In this case, the rat has to complete the response requirement (FR 5) on the right lever to end the initial link. After a 2-s delay, the terminal link begins. Responses on the left lever are recorded but have no programmed consequence. Completing the response requirement (FR 3) on the right lever results in delivery of one sucrose-based pellet. In trial 2, responses on the right lever during the initial link are recorded but have no programmed consequences. The rat has to respond on the left lever to advance to the terminal link. During the terminal link, responses on the right lever are recorded but have no programmed consequences. Completing the response requirement on the left lever results in probabilistic delivery of four sucrose-based pellets. For each rat, the active lever (i.e., the lever that ends the initial link and the lever that leads to reinforcement) is pseudo-randomized across trials, such that each lever leads to reinforcement on an equal number of trials (5 trials each per block; 25 total trials across the session). Abbreviations: HL = house light; ITI = inter-trial interval; LL = left lever; LSL = left stimulus light; OA = odds against (note: odds against = [1/probability]-1); RR = right lever; RSL = right stimulus light.

Figure 2.

Example session from subject 503 during the initial link of the concurrent chains procedure (dependent schedule component) following administration of vehicle (for methylphenidate). (a) Trial-by-trial (rows) and block-by-block (columns) breakdown during the dependent schedule, where the right lever is associated with the small, certain reinforcer, and the left lever is associated with the large, uncertain reinforcer. Within each trial, only one reinforcer is scheduled, represented by bolded text with (+) sign. The number below LR/SS labels represents the number of responses made on that lever (note: LR = large, risky reinforcer; SS = small, safe reinforcer). Numbers that are under bolded labels with (+) signs represent forced responses (i.e., rats have to respond on this lever to advance from the initial link to the terminal link). Numbers that are under un-bolded labels with (−) signs represent choice responses (i.e., responses on this lever are not necessary to advance the trial to the terminal link). (b) Graphical representation of the number of choice responses for the LR and the SS across blocks as a function of odds against (OA). (c) Graphical representation of the proportion of responses for the LR based upon LR and SS choice responses; the line indicates the best fit of the exponential discounting function. The A and h parameter estimate, as well as R², are listed on the figure. Note: figure is adapted from Beckmann et al. (in press).

Figure 3.

Mean (±SEM) proportion of responses for the large, uncertain reinforcer as a function of odds against (OA) averaged across sessions 1–3, sessions 21–23, and sessions 41–43 (a). Lines are NLME-determined best fits of the exponential discounting function. Mean (±SEM) A (b) and h (c) parameter estimates across the sessions depicted in panel a. *p < .05, relative to sessions 1–3. #p < .05, relative to sessions 1–3 and sessions 21–23.

Figure 4.

Mean (±SEM) proportion of responses for the large, uncertain reinforcer during the initial link as a function of odds against (OA) across each dose of amphetamine (a), methylphenidate (b), and methamphetamine (c). Lines are NLME-determined best fits of the exponential discounting function. Mean (±SEM) A parameter estimates derived from the exponential function across each dose of amphetamine (d), methylphenidate (e), and methamphetamine (f). Mean (±SEM) h parameter estimates derived from the exponential function across each dose of amphetamine (g), methylphenidate (h), and methamphetamine (i). *p < .05, relative to vehicle. Note: in panels d-i, V = vehicle.

Figure 5.

Mean (±SEM) proportion of responses for the large, uncertain reinforcer as a function of odds against (OA) in the current experiment and in two of our previous studies (Yates et al. 2016; Yates, Prior, et al. 2018) (a). Lines are NLME-determined best fits of the exponential discounting function. Mean (±SEM) A (b) and h (c) parameter estimates across the experiments depicted in panel a. *p < .05, relative to the current experiment and the Yates, Prior, et al. (2018) study (b), and relative to the Yates, Prior, et al. (2018) and the Yates et al. (2016) studies (c).