A behavioral economic analysis of cocaine and remifentanil self-administration in rhesus monkeys

Wade-Galuska, Tammy; Winger, Gail; Woods, James H.

doi:10.1007/s00213-007-0858-0

Cited by 32 publications

(35 citation statements)

References 28 publications

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“…It was hypothesized that monkeys would mix cocaine and remifentanil within a session, and that they would adjust their responding to maintain a ratio of cocaine:remifentanil intake reflective of an optimal reinforcement set point. Consistent with previous reports, cocaine and remifentanil functioned as reinforcers in all subjects (e.g., Freeman and Woolverton 2011; Wade-Galuska et al 2007; Winger et al 2006), and monkeys responded on both levers when cocaine and remifentanil were concurrently available. While these results indicate that monkeys would co-administer cocaine and an opioid, there was no indication that they would adjust their response rates to maintain an optimal ratio of cocaine:remifentanil intake.…”

Section: Discussionsupporting

confidence: 89%

“…Behavioral economics uses demand-curve analysis to describe reinforcer consumption across a range of response requirements (Hursh and Silberberg 2008). Results from this approach indicate that cocaine-opioid mixtures were not more effective reinforcers than at least one of the single drugs (Mattox et al 1997; Wade-Galuska et al 2007; Winger et al 2006). In PR studies, where the response requirement systematically increases within session, cocaine-opioid mixtures were more potent reinforcers than the single drugs, evidenced by leftward shifts in the dose-response functions for the mixtures (Duvauchelle et al 1998; Ranaldi and Munn 1998; Rowlett et al 1998, 2005, 2007; Rowlett and Woolverton 1997; Woolverton et al 2008, but see Ward et al 2005).…”

Section: Introductionmentioning

confidence: 97%

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Self-administration of cocaine and remifentanil by monkeys under concurrent-access conditions

2014

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Rationale Cocaine and opioids are often co-abused. Laboratory research has focused largely on the reinforcing effects of mixtures of drugs relative to the drugs alone. Less research has examined drug mixing by the subject under concurrent-access conditions. Objective Self-administration of various doses of cocaine and remifentanil was examined under concurrent-access conditions. It was hypothesized that if cocaine and opioid combinations were more effective reinforcers than the single drugs, subjects would mix the two drugs by adjusting their responding to cocaine and opioid alternatives to maintain an optimal ratio of cocaine:remifentanil intake. Method Three male rhesus monkeys were allowed to self-administer cocaine (0.05–0.2 mg/kg/inj) or saline on one lever and remifentanil (0.05–0.4 µg/kg/inj) or saline on the other lever under concurrent FR 10 schedules. Daily sessions lasted 2-h, and there was a 1-s timeout after every 10-s injection. Results When saline and drug were concurrently available, responding on the saline-associated lever was low relative to the drug alternative. When cocaine and remifentanil were concurrently available, both drugs were self-administered above saline levels. Cocaine intake decreased and remifentanil intake increased as a function of the remifentanil dose that was available. Conversely, cocaine intake and remifentanil intake did not change systematically as a function of the cocaine dose that was available. Conclusion Monkeys will mix cocaine and an opioid when the two drugs are available concurrently. However, there was no indication that monkeys titrated drug-intake to maintain an optimal ratio of intake of the two compounds.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 97%

Self-administration of cocaine and remifentanil by monkeys under concurrent-access conditions

2014

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“…Appetitive behavior is assessed later in the session by determining the lowest unit dose (ie, highest unit price) that maintains consumption. Typically in self-administration studies, price is manipulated by holding a drug dose constant and increasing the response requirement (Cosgrove and Carroll, 2002;Wade-Galuska et al, 2007); however, fixing the response requirement and decreasing the available unit dose accomplishes the same thing (Bickel et al, 1990). Here, the decreasing series of unit doses resulted in an ascending series of unit prices (2.4, 4.2, 7.5, 13, 24, 40, 77, 133, 244, 416, and 750 responses/mg).…”

Section: Figurementioning

confidence: 99%

The Motivation to Self-Administer is Increased After a History of Spiking Brain Levels of Cocaine

Zimmer

Oleson

Roberts

2012

Neuropsychopharmacol

141

205

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Recent attempts to model the addiction process in rodents have focused on cocaine self-administration procedures that provide extended daily access. Such procedures produce a characteristic loading phase during which blood levels rapidly rise and then are maintained within an elevated range for the duration of the session. The present experiments tested the hypothesis that multiple fastrising spikes in cocaine levels contribute to the addiction process more robustly than constant, maintained drug levels. Here, we compared the effects of various cocaine self-administration procedures that produced very different patterns of drug intake and drug dynamics on Pmax, a behavioral economic measure of the motivation to self-administer drug. Two groups received intermittent access (IntA) to cocaine during daily 6-h sessions. Access was limited to twelve 5-min trials that alternated with 25-min timeout periods, using either a hold-down procedure or a fixed ratio 1 (FR1). Cocaine levels could not be maintained with this procedure; instead the animals experienced 12 fast-rising spikes in cocaine levels each day. The IntA groups were compared with groups given 6-h FR1 long access and 2-h short access sessions and two other control groups. Here, we report that cocaine self-administration procedures resulting in repeatedly spiking drug levels produce more robust increases in Pmax than procedures resulting in maintained high levels of cocaine. These results suggest that rapid spiking of brain-cocaine levels is sufficient to increase the motivation to self-administer cocaine.

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“…These aspects of behavior have included (1) rate of responding, (2) the number of responses (or highest ratio completed) on progressive ratio schedules of reinforcement (for review, see Arnold and Roberts 1997;Stafford et al 1998), (3) choice between drug and non-drug reinforcers to reveal in a relative manner how effective a reinforcer is (e.g., Aigner and Balster 1978;Nader and Woolverton 1991;Anderson et al 2002;Negus 2003;Gasior et al 2005), (4) choice to determine which dose in a series is more preferred (Johanson and Schuster 1975;Llewellyn et al 1976;Lynch et al 1998;Ward et al 2005), (5) behavioral economic measures of unit price and demand curves (DeGrandpre et al 1993;Bickel et al 2000;Rowlett et al 2002;Johnson and Bickel 2006;Winger et al 2006;Wade-Galuska et al 2007), and (6) other aspects of behavior such as the study of response acquisition, relative persistence of responding, or sensitivity to punishment (e.g., Grove and Schuster 1974;Carroll and Lac 1997;Meisch 2000;DerocheGamonet et al 2004;Negus 2005). The general, but simplified, conclusion from this body of literature is that the higher the drug dose, the more efficacious, preferred, or effective that dose will function as a reinforcer.…”

Section: Introductionmentioning

confidence: 99%

Cocaine self-administration on a hold-down schedule of reinforcement in rats

et al. 2008

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Stability of responding under these schedule conditions was acquired quickly. This schedule of reinforcement may be useful for comparing across drug classes, can be extended for use with other types of responses and reinforcers, and may be more representative of the natural world where response-reinforcer contingencies are more likely to be experienced along continuous, rather than discrete, dimensions.

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A behavioral economic analysis of cocaine and remifentanil self-administration in rhesus monkeys

Abstract: Polydrug use involving stimulants and opiates may occur because these drugs are highly substitutable.

Cited by 32 publications

References 28 publications

Self-administration of cocaine and remifentanil by monkeys under concurrent-access conditions

Self-administration of cocaine and remifentanil by monkeys under concurrent-access conditions

The Motivation to Self-Administer is Increased After a History of Spiking Brain Levels of Cocaine

Cocaine self-administration on a hold-down schedule of reinforcement in rats

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