Rationale Drug effects on delay discounting are thought to reflect changes in sensitivity to reinforcer delay, although other behavioral mechanisms might be involved. One strategy for revealing the influence of different behavioral mechanisms is to alter features of the procedures in which they are studied. Objective This experiment examined whether the order of delay presentation under within-session delay discounting procedures impacts drug effects on discounting. Methods Rats responded under a discrete-trial choice procedure in which responses on one lever delivered 1 food pellet immediately and responses on the other lever delivered 3 food pellets either immediately or after a delay. The delay to the larger reinforcer (0, 4, 8, 16, and 32 s) was varied within session and the order of delay presentation (ascending or descending) varied between groups. Results Amphetamine (0.1–1.78 mg/kg) and methylphenidate (1.0–17.8 mg/kg) shifted delay functions upward in the ascending group (increasing choice of the larger reinforcer) and downward in the descending group (decreasing choice of the larger reinforcer). Morphine (1.0–10.0 mg/kg) and delta-9-tetrahydrocannabinol (0.32–5.6 mg/kg) tended to shift the delay functions downward, regardless of order of delay presentation, thereby reducing choice of the larger reinforcer, even when both reinforcers were delivered immediately. Conclusion The effects of amphetamine and methylphenidate under delay discounting procedures differed depending on the order of delay presentation indicating that drug-induced changes in discounting were due, in part, to mechanisms other than altered sensitivity to reinforcer delay. Instead, amphetamine and methylphenidate altered responding in a manner consistent with increased behavioral perseveration.

Whether stimulant drugs like amphetamine increase or decrease choice of larger delayed reinforcers over smaller immediately available reinforcers under delay discounting procedures can depend on several factors, including the order in which delay is presented. This study examined whether the order of delay presentation impacts drug effects on discounting in rats (n=8) trained and tested under an ascending order, a descending order, as well as under a fixed delay condition. Responses on one lever delivered 1 food pellet immediately and responses on the other lever delivered 3 food pellets immediately or after a delay (4–32 s). In Experiment 1, the delay to the larger reinforcer varied within session and the order of delay presentation (ascending or descending) varied across conditions. In Experiment 2, the same delay value was presented in all blocks of the session (i.e., delay was fixed), and delay varied across phases. Under the ascending order of delay, amphetamine (0.32–1.78 mg/kg) increased choice of the larger reinforcer in some rats and decreased choice in others. In the same rats responding under the descending and fixed delay conditions, amphetamine markedly decreased choice of the larger reinforcer even in the component associated with no delay. In some subjects, the effects of amphetamine differed depending on the manner in which delay was presented, indicating that drug-induced changes in performance were due, in part, to mechanisms other than altered sensitivity to reinforcer delay. These results also suggest that a history of responding under both orders of delay presentation can modulate drug effects.

We examined the effects of acute administration of morphine and amphetamine prior to and during daily morphine administration in rats responding under a five-choice serial reaction time task. Rats (n = 5) were trained to detect a brief flash of light presented randomly in one of five response holes; responding in the target hole delivered food, whereas responding in the wrong hole or responding prior to illumination of the target stimulus (premature response) initiated a timeout. Premature responding served as an index of motor impulsivity. KEY RESULTSAdministered acutely, morphine (0.1-10 mg·kg À1 , i.p.) increased omissions and modestly, although not significantly, premature responding without affecting response accuracy; amphetamine (0.1-1.78 mg·kg À1 , i.p.) increased premature responding without changing omissions or response accuracy. After 3 weeks of 10 mg·kg À1 ·day À1 morphine, tolerance developed to its effects on omissions whereas premature responding increased approximately fourfold, compared with baseline. Effects of amphetamine were not significantly affected by daily morphine administration. CONCLUSIONS AND IMPLICATIONSThese data suggest that repeated administration of morphine increased effects of morphine on motor impulsivity, although tolerance developed to other effects, such as omissions. To the extent that impulsivity is a risk factor for drug abuse, repeated administration of μ opioid receptor agonists, for recreational or therapeutic purposes, might increase impulsivity and thus the risk for drug abuse.Abbreviations 5-CSRTT, 5-choice serial reaction time task

In rats, the discriminative stimulus effects of direct‐ (e.g., quinpirole) and indirect‐ (e.g., cocaine) acting dopamine receptor agonists are mediated by multiple dopamine receptor subtypes and the relative contribution of D2 and D3 receptors to these effects can be altered by manipulating feeding conditions (e.g., food restriction). In these studies two‐lever discriminations were trained with either 10.0 mg/kg cocaine or 0.032 mg/kg quinpirole in free‐fed and food‐restricted mice using a fixed ratio 10 schedule of reinforcement for 50% sweetened condensed milk. Although free‐fed mice responded at lower rates under training conditions and were more sensitive to the rate suppressant effects of their respective training drugs, feeding condition did not affect the acquisition of either discrimination and did not alter the potencies of cocaine or quinpirole to increase cocaine‐ and quinpirole‐appropriate responding, respectively. These novel discriminations will allow for the identification of the specific receptors that mediate the interoceptive effects of cocaine and quinpirole and will serve as the basis for future studies of the influence of diet on drug effects in mice. CPF is supported by a NIDA Senior Scientist Award (K05 DA017918).