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

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).

Effects of GluN2B-selective antagonists on delay and probability discounting in male rats: Modulation by delay/probability presentation order.

The contribution of the GluN2B subunit of the NMDA receptor to impulsivity has recently been examined. Ro 63-1908, a highly selective antagonist for the GluN2B, decreases impulsive choice. Because the order in which delays are presented modulates drug effects in discounting procedures, one goal of the current study was to determine the effects of Ro 63-1908 in delay discounting procedures in which the delays to obtaining the large reinforcer either increase or decrease across the session. We also determined if Ro 63-1908 differentially alters risky choice in probability discounting procedures that use ascending/descending schedules. Male rats were trained in either delay (n = 24) or probability (n = 24) discounting in which the delay to/odds against reinforcement were presented in either ascending or descending order (n = 12 each schedule). Following training, rats received the GluN2B antagonists Ro 63-1908 (0-1.0 mg/kg) and CP-101,606 (0-3.0 mg/kg). In delay discounting, Ro 63-1908 (1.0 mg/kg), but not CP-101,606, decreased choice for the large reinforcer, but only when the delays decreased across the session. In probability discounting, Ro 63-1908 (0.3 mg/kg)/CP-101,606 (1.0 mg/kg) increased choice for the large reinforcer when the probability of obtaining this alternative decreased across the session, but Ro 63-1908 (1.0 mg/kg)/CP-101,606 (3.0 mg/kg) decreased choice when the probabilities increased. These results show that the GluN2B is a mediator of impulsive/risky choice, but the effects of GluN2B antagonists are dependent on the order in which delays/probabilities are presented. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Effects of Group I metabotropic glutamate receptor antagonists on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting task in rats: Contribution of delay presentation order.

Metabotropic glutamate receptor 1 (mGluR1) blockade has been shown to decrease impulsive choice, as measured in delay discounting. However, several variables are known to influence an animal's discounting, including sensitivity to delayed reinforcement and sensitivity to reinforcer magnitude. The goal of this experiment was to determine the effects of mGluR1, as well as mGluR5, antagonism on these parameters. Forty Sprague Dawley rats were trained in delay discounting, in which consistently choosing a small, immediate reward reflects impulsive choice. For half of the rats, the delay to the large reinforcer increased across blocks of trials, whereas the delay decreased across the session for half of the rats. Following training, half of the rats received injections of the mGluR1 antagonist JNJ 16259685 (JNJ; 0, 0.1, 0.3, or 1.0mg/kg; i.p), and half received injections of the mGluR5 antagonist MPEP (0, 1.0, 3.0, or 10.0mg/kg; i.p.). Administration of JNJ increased sensitivity to delayed reinforcement (i.e., promoted impulsive choice), regardless of which schedule was used. However, the order in which delays were presented modulated the effects of JNJ on sensitivity to reinforcer magnitude. Specifically, JNJ decreased sensitivity to reinforcer magnitude in rats trained on the descending schedule only. MPEP did not alter sensitivity to reinforcer magnitude or sensitivity to delayed reinforcement. These results show that mGluR1 is an important mediator of impulsive choice, and they provide further evidence that delay order presentation is an important variable that influences drug effects in delay discounting.

Effects of N-methyl-D-aspartate receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure.

RATIONALE: The N-methyl-D-aspartate (NMDA) receptor has been recently identified as an important mediator of impulsive choice, as assessed in delay discounting. Although discounting is independently influenced by sensitivity to reinforcer magnitude and delayed reinforcement, few studies have examined how NMDA receptor ligands differentially affect these parameters. OBJECTIVES: The current study examined the effects of various NMDA receptor ligands on sensitivity to reinforcer magnitude and delayed reinforcement in a delay-discounting procedure. METHODS: Following behavioral training, rats received treatments of the following NMDA receptor ligands: the uncompetitive antagonists ketamine (0, 1.0, 5.0, or 10.0 mg/kg; i.p.), MK-801 (0, 0.003, 0.01, or 0.03 mg/kg; s.c.), and memantine (0, 2.5, 5.0, or 10.0 mg/kg; i.p.), the competitive antagonist CGS 19755 (0, 5.0, 10.0, or 20.0 mg/kg; s.c.), the non-competitive NR2B subunit-selective antagonist ifenprodil (0, 1.0, 3.0, or 10.0 mg/kg; i.p), and the partial agonist D-cycloserine (0, 3.25, 15.0, or 30.0 mg/kg; s.c.). RESULTS: When an exponential model was used to describe discounting, CGS 19755 (5.0 mg/kg) increased impulsive choice without altering sensitivity to reinforcer magnitude. Conversely, ketamine (10.0 mg/kg), memantine (5.0 mg/kg), and ifenprodil (10.0 mg/kg) decreased sensitivity to reinforcer magnitude without altering impulsive choice. MK-801 and D-cycloserine did not alter delay-discounting performance, although two-way ANOVA analyses indicated D-cycloserine (15.0 mg/kg) decreased impulsive choice. CONCLUSIONS: The behavioral changes observed in delay discounting following administration of NMDA receptor antagonists do not always reflect an alteration in impulsive choice. These results emphasize the utility in employing quantitative methods to assess drug effects in delay discounting.