The contribution of the GluN2B subunit of the NMDA receptor to impulsive/risky choice has recently been examined. Ro 63–1908, a highly selective antagonist for GluN2B-containing NMDA receptors, 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, 0.1, 0.3, 1.0 mg/kg) and CP-101,606 (0, 0.3, 1.0, 3.0 mg/kg) in a counterbalanced order. 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.

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.

The glutamatergic system has been identified as an important mediator of risky choice. However, previous studies have focused primarily on ionotropic glutamate receptors (e.g., NMDA receptors). Little research has examined the contribution of metabotropic glutamate receptors (mGluRs) on risky choice. The goal of the current experiment was to determine the effects of mGluR 1 and mGluR 5 antagonism on risky choice as assessed in probability discounting (PD). Male Sprague Dawley rats (n = 24) were trained in PD, in which consistently choosing a large, probabilistic reward (LR) reflects risky choice. For half of the rats, the odds against (OA) receiving the LR increased across blocks of trials, whereas the OA decreased across the session for half of the rats. Following training, rats received injections of the mGluR1 antagonist JNJ 16259685 (JNJ; 0, 0.1, 0.3, or 1.0 mg/kg; i.p) and the mGluR5 antagonist MTEP (0, 1.0, 3.0, or 10.0 mg/kg; i.p.). Regardless of which schedule was used, JNJ and MTEP decreased preference for the LR when its delivery was guaranteed. In contrast to delay discounting, in which blocking the mGluR 1 has been shown to alter impulsive choice, these results show that the Group I mGluR family does not selectively alter risky choice. Instead, blocking these receptors appears to impair discriminability of reinforcers of varying magnitudes in PD. Keywordsrisky choice; probability discounting; sensitivity to probabilistic reinforcement; discriminability of reinforcer magnitude; metabotropic glutamate receptor; rat Probability discounting (PD) is often used to measure risky choice in animals (see [1] for a recent review). Recent evidence has implicated the glutamatergic system as being an important mediator of PD. The N-methyl-D-aspartate (NMDA) receptor antagonists MK-801 and ketamine differentially alter performance in this task, as MK-801 decreases sensitivity to probabilistic reinforcement (i.e., increases risky choice), whereas ketamine