The association between risky decision making and cocaine conditioned place preference is moderated by sex.

BACKGROUND: Excessive risk taking is a characteristic trait of several psychiatric conditions, including substance use disorders. High risk-taking (HiR) rats self-administer more cocaine compared to low risk-taking (LoR) rats. However, research has not determined if risk taking is associated with enhanced cocaine conditioned place preference (CPP). METHODS: Male and female Sprague Dawley rats (n = 48 each sex) were first tested in the risky decision task (RDT), in which a response on one lever resulted in safe delivery of one food pellet, and a response on a different lever resulted in delivery of two pellets and probabilistic delivery of foot shock. Following RDT training, rats were tested for cocaine CPP. The first session was a pretest that measured rats' preference for three compartments that provided different visual and tactile cues. Rats then learned to associate one compartment with cocaine (either 10.0 mg/kg or 20.0 mg/kg; i.p.) and one compartment with saline (1.0 ml/kg; i.p.) across eight conditioning sessions. Finally, rats explored all three compartments in a drug-free state. RESULTS: Sex significantly moderated the association between risky decision making and cocaine CPP. While increased risk aversion was somewhat positively associated with cocaine CPP in males, increased risk taking was positively correlated with cocaine CPP in females. CONCLUSIONS: These results highlight the moderating role of sex on the relationship between risky decision making and cocaine reward.

Differential effects of glutamate N-methyl-D-aspartate receptor antagonists on risky choice as assessed in the risky decision task.

RATIONALE: Risky choice can be measured using the risky decision task (RDT). In the RDT, animals choose between a large, risky option that is paired with probabilistic foot shock and a small, safe option that is never paired with shock. To date, studies examining the neurochemical basis of decision-making in the RDT have focused primarily on the dopaminergic system but have not focused on the glutamatergic system, which has been implicated in risky decision-making. OBJECTIVES: Because glutamate is known to play a critical role in decision-making, we wanted to determine the contribution of the glutamatergic system to performance in the RDT. METHODS: In the experiment, 32 rats (16 male; 16 female) were tested in the RDT. The probability of receiving a foot shock increased across the session (ascending schedule) for half of the rats but decreased across the session (descending schedule) for half of the rats. Following training, rats received injections of the N-methyl-D-aspartate (NMDA) receptor competitive antagonist CGS 19755 (0, 1.0, 2.5, 5.0 mg/kg; s.c.) and the GluN2B-selective antagonist Ro 63-1908 (0, 0.1, 0.3, 1.0 mg/kg; s.c.). RESULTS: CGS 19755 (2.5 and 5.0 mg/kg) increased risky choice in males and females trained on the ascending schedule. Ro 63-1908 (1.0 mg/kg) decreased risky choice, but only in male rats trained on the ascending schedule. CONCLUSIONS: Although NMDA receptor antagonists differentially alter risky choice in the RDT, the current results show that NMDA receptors are an important mediator of decision-making involving probabilistic delivery of positive punishment.

Pair housing, but not using a controlled reinforcer frequency procedure, attenuates the modulatory effect of probability presentation order on amphetamine-induced changes in risky choice.

Probability discounting is often measured with independent schedules. Independent schedules have several limitations, such as confounding preference for one alternative with frequency of reward presentation and generating ceiling/floor effects at certain probabilities. To address this potential caveat, a controlled reinforcer frequency schedule can be used, in which the manipulandum that leads to reinforcement is pseudo-randomly determined before each trial. This schedule ensures subjects receive equal presentations of the small and large magnitude reinforcers across each block of trials. A total of 24 pair-housed and 11 individually housed female Sprague Dawley rats were tested in a controlled reinforcer frequency procedure. For half of the rats, the odds against (OA) receiving the large magnitude reinforcer increased across the session (ascending schedule); the OA decreased across the session for half of the rats (descending schedule). Following training, rats received treatments of amphetamine (AMPH; 0, 0.25, 0.5, 1.0 mg/kg; s.c.). For pair-housed rats, AMPH (0.5 mg/kg) increased risky choice, regardless of probability presentation order, whereas a higher dose of AMPH (1.0 mg/kg) decreased discriminability of reinforcer magnitude for rats trained on the descending schedule only. For individually housed rats, probability presentation order modulated the effects of AMPH on probability discounting, as AMPH (0.25 and 0.5 mg/kg) increased risky choice in rats trained on the ascending schedule but not on the descending schedule. These results show that pair-housing animals, but not using a controlled reinforcer frequency procedure, attenuates the modulatory effects of probability presentation order on drug effects on risky choice.

Effects of d-amphetamine and MK-801 on impulsive choice: Modulation by schedule of reinforcement and delay length.

Procedural modifications can modulate drug effects in delay discounting, such as signaling the delay to reinforcement and altering the order in which delays are presented. Although the schedule of reinforcement can alter the rate at which animals discount a reinforcer, research has not determined if animals trained on different schedules of reinforcement are differentially affected by pharmacological manipulations. Similarly, research has not determined if using different delays to reinforcement can modulate drug effects in delay discounting. Male Sprague Dawley rats (n = 36) were split into four groups and were trained in a delay-discounting procedure. The schedule of reinforcement (fixed ratio [FR] 1 vs. FR 10) and delays to reinforcement (0, 5, 10, 20, and 50 s vs. 0, 10, 30, 60, 100 s) were manipulated for each group. Following behavioral training, rats were treated with d-amphetamine (0, 0.25, 0.5, and 1.0 mg/kg) and MK-801 (0, 0.03, and 0.06 mg/kg). Results showed that amphetamine decreased impulsive choice when a FR 1 schedule was used, but only when the short delay sequence was used. Conversely, amphetamine decreased impulsive choice when a FR 10 schedule was used, but only when rats were trained on the long delay sequence. MK-801 decreased impulsive choice in rats trained on a FR 1 schedule, regardless of delay sequence, but did not alter choice in rats trained on a FR 10 schedule. These results show that schedule of reinforcement and delay length can modulate drug effects in delay discounting.