Effects of GluN2B-selective Antagonists on Delay and Probability Discounting in Male Rats: Modulation by Delay/Probability Presentation Order

摘要

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.