Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys

Woolverton, William L.; Anderson, Karen G.

doi:10.1007/s00213-006-0355-x

Cited by 53 publications

(62 citation statements)

References 36 publications

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“…Nondrug alternative reinforcers decrease drug selfadministration using either choice procedures or noncontingent direct exposure to an alternative rewarding stimulus (Carroll et al, 1989;Woolverton and Anderson, 2006). In humans, prosocial behaviors such as physical activity and engaging in high sensation experiences may be effective in reducing drug use.…”

Section: Implications For Prevention and Treatment Of Drug Abusementioning

confidence: 99%

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

2013

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Section: Implications For Prevention and Treatment Of Drug Abusementioning

confidence: 99%

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

2013

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“…Few medications have selectively and robustly shifted cocaine self-administration, but it may be that this behavior would be more sensitive to medication effects if alternative reinforcers were immediate (as the cocaine reinforcer is). For example, non-human primates responding to receive either cocaine or an alternative reinforcer chose less cocaine if the delivery of the alternative reinforcer was immediate compared to when the delivery of the alternative reinforcer was delayed (Woolverton and Anderson 2006). In most human laboratory procedures, the alternative reinforcer is not available until completion of the study.…”

Section: Alternative Reinforcersmentioning

confidence: 99%

Controversies in translational research: drug self-administration

2008

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Rationale Laboratory animal and human models of drug self-administration are used to evaluate potential pharmacotherapies for drug abuse, yet the utility of these models in predicting clinically useful medications is variable. Objective The objective of this study was to track how antagonist, agonist, and partial agonist medication approaches influence heroin and cocaine self-administration by rodents, non-human primates, and humans and to compare these results to clinical outcomes. Results Across species, heroin self-administration was decreased by all three medication approaches, paralleling their demonstrated clinical utility. The heroin data emphasize the importance of assessing a medication's abuse liability preclinically to predict medication abuse and compliance and of considering subject characteristics (e.g., opioid dependence) when interpreting medication effects. For cocaine, the effects of ecopipam, modafinil, and aripiprazole were consistent in the laboratory and clinic, provided that the medications were administered repeatedly before self-administration sessions. Modafinil attenuated cocaine's reinforcing effects in the human laboratory and improved treatment outcome, while ecopipam and aripiprazole increased the reinforcing effects of cocaine and do not appear promising in the clinic. Conclusions The self-administration model has reliably identified medications to treat opioid dependence, and the recent data with modafinil suggest that the human laboratory model also identifies medications to treat cocaine dependence. There have been numerous false positives when subjective effects are the primary outcome measure, but not when self-administration is the outcome. Factors relevant to the predictive validity of self-administration procedures include medication maintenance and the concurrent assessment of a range of behaviors to determine abuse liability and the specificity of effect.Keywords Cocaine . Opioid . Naloxone . Dopamine receptor . Drug abuse . Model . Monkey . Human . Reinforcement Laboratory testing of potential pharmacotherapies for drug abuse is an essential component of medication development. Although well-designed clinical trials are the standard by which the efficacy of a new medication is assessed, clinical trials test the effects of a potential treatment medication on a broad sample of patients, which is both costly and potentially risky. Before exposing a large number of treatment seekers to a medication, there needs to be both a strong scientific rationale for combining the medication with a drug of abuse as well as a demonstration that the co-administration of the medication and the abused drug is safe and selectively modifies the behavior of interest: drug taking.Models of drug self-administration in rodents, nonhuman primates, and humans have been used to evaluate the effects of candidate medications for the treatment of drug dependence. The self-administration model provides Psychopharmacology (2008) meaningful behavioral data on the safety and efficacy of potentia...

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“…For example, imposing a delay between completion of the response requirement and delivery of an infusion of cocaine decreases response rates in rhesus monkeys lever pressing under a single-response self-administration procedure (Beardsley and Balster, 1993). More recently, researchers (Anderson and Woolverton, 2003;Woolverton and Anderson, 2006;Woolverton et al, 2007) showed that delay impacts self-administration of cocaine under concurrent choice procedures. For example, when given a choice between smaller doses of cocaine delivered immediately and a large dose of cocaine delivered after a delay, rhesus monkeys responded less for the large, delayed dose and more for the smaller, immediately available doses (Woolverton and Anderson, 2006;Woolverton et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

“…More recently, researchers (Anderson and Woolverton, 2003;Woolverton and Anderson, 2006;Woolverton et al, 2007) showed that delay impacts self-administration of cocaine under concurrent choice procedures. For example, when given a choice between smaller doses of cocaine delivered immediately and a large dose of cocaine delivered after a delay, rhesus monkeys responded less for the large, delayed dose and more for the smaller, immediately available doses (Woolverton and Anderson, 2006;Woolverton et al, 2007). Woolverton et al (2007) further demonstrated that decreased choice of the large, delayed dose of cocaine was well described by a hyperbolic discounting function in a manner comparable to other types of reinforcers (Mazur, 1987), suggesting that choice involving drug and nondrug reinforcers is likely under the control of similar behavioral processes.…”

Section: Introductionmentioning

confidence: 99%

Effect of Delay on Self-Administration of Remifentanil under a Drug Versus Drug Choice Procedure in Rhesus Monkeys

Maguire

Gerak

2013

J Pharmacol Exp Ther

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Drug abuse can be conceptualized as excessive choice of drug over other reinforcers, and factors that affect drug taking can be examined experimentally using choice procedures. This study examined the impact of reinforcer delay on self-administration of the m-opioid receptor agonist remifentanil in rhesus monkeys (n 5 4) lever pressing under a concurrent fixed-ratio 30 schedule. Responding on either lever delivered an intravenous infusion of either remifentanil or saline. Dose-effect curves were first determined when responding on one lever delivered remifentanil and responding on a second lever delivered saline. Monkeys then chose between two doses of remifentanil, and delay to delivery of the large dose was varied systematically. Responding for remifentanil (0.01-1.0 mg/kg/infusion) increased dose-dependently when the alternative was saline or a dose of remifentanil. Delaying delivery of the large dose of remifentanil by 30, 60, 120, or 240 seconds increased responding for smaller, immediately available doses (0.01-0.1 mg/kg/infusion) and, in some cases, increased responding for doses of remifentanil that did not maintain responding when the alternative was saline. These data demonstrate that delaying the delivery of an opioid receptor agonist can significantly affect its reinforcing effectiveness. The imposition of a delay reduces the effectiveness of large doses of drug to maintain responding and increases the effectiveness of immediately available commodities, including smaller doses of drug. Increased reinforcing effectiveness of smaller doses of drug in the context of other delayed reinforcers might contribute to the development and maintenance of opioid abuse.

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Effects of delay to reinforcement on the choice between cocaine and food in rhesus monkeys

Abstract: This experiment demonstrates that the choice between cocaine and a non-drug or drug alternative can be modified by increasing the interval between behavior and drug injection. Overall, the results are consistent with a temporal discounting model of drug choice.

Cited by 53 publications

References 36 publications

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

Individual Differences and Social Influences on the Neurobehavioral Pharmacology of Abused Drugs

Controversies in translational research: drug self-administration

Effect of Delay on Self-Administration of Remifentanil under a Drug Versus Drug Choice Procedure in Rhesus Monkeys

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