Self-administration of psychoactive substances by the monkey

Deneau, Gerald A.; Yanagita, Tomoji; Seevers, M. H.

doi:10.1007/bf00405254

Cited by 775 publications

(282 citation statements)

References 7 publications

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“…This finding reproduces previous research on prolonged or unlimited access to opiate self-administration in rats (Bozarth and Wise, 1985;Ahmed et al, 2000;Morgan et al, 2002;Walker et al, 2003;Kenny et al, 2006;Chen et al, 2006;, monkeys (Deneau et al, 1969;Woods and Schuster, 1971) and humans (Wikler, 1952). After escalation, increasing heroin prices decreased heroin consumption in both groups of animals.…”

Section: Discussionsupporting

confidence: 89%

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Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Lenoir

Ahmed

2007

Neuropsychopharmacol

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Escalation of drug consumptionFa hallmark of addictionFhas been hypothesized to be associated with a relative devaluation of alternative nondrug rewards and thus with a decrease in their ability to compete with or to substitute for the drug. In a behavioral economic framework, decreased substitutability of nondrug rewards for drug would explain why drug consumption is behaviorally dominant and relatively resistant to change (eg price-inelastic) in drug-addicted individuals. The goal of the present study was to test this hypothesis using a validated rat model of heroin intake escalation. Escalation was precipitated by long (6 h, long access (LgA)), but not short (1 h, short access (ShA)), daily access to i.v. heroin self-administration. After escalation, the effects of price (ie fixed-ratio value) on heroin consumption were assessed under two alternative reward conditions: in the presence or absence of a nondrug substitute for heroin (ie four freely available chow pellets). As expected, escalated heroin consumption by LgA rats was less sensitive to price than heroin consumption by ShA rats, showing that heroin had acquired greater reinforcing strength during escalation. However, supplying a substitute during access to heroin was sufficient to reverse this post-escalation increase in the reinforcing effectiveness of heroin. Thus, escalated heroin consumption is not associated with a decreased sensitivity to competing nondrug rewards. Escalated drug use may therefore persist, not so much because of a relative devaluation of nondrug substitutes, but because of a loss or reduction of their availability.

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Section: Discussionsupporting

confidence: 89%

“…Based on previous research on continuous access to drug self-administration (Deneau et al, 1969;Johanson et al, 1976;Bozarth and Wise, 1985;Wolffgramm, 1991), we and others have recently developed and begun to validate an animal model of the transition to escalated drug use (reviewed in Ahmed, 2005). Differential access to i.v.…”

Section: Introductionmentioning

confidence: 99%

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Lenoir

Ahmed

2007

Neuropsychopharmacol

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“…in order to receive a drug. This type of study largely grew out of procedures developed in laboratory animals during the early 1960's (e.g., Deneau et al, 1969;Thompson and Schuster, 1964). Soon thereafter, the study of drug self-administration via operant responding was initiated in human research volunteers (Mendelson and Mello, 1966).…”

Section: Non-verbal Operant Proceduresmentioning

confidence: 99%

The role of human drug self-administration procedures in the development of medications

Comer

Ashworth²,

Foltin

et al. 2008

Drug and Alcohol Dependence

136

148

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The purpose of this review is to illustrate the utility and value of employing human self-administration procedures in medication development, including abuse liability assessments of novel medications and evaluation of potential pharmacotherapies for substance use disorders. Traditionally, human abuse liability testing has relied primarily on subjective reports describing drug action by use of questionnaires; similarly, drug interactions between putative treatment agents and the drugs of abuse have relied on these measures. Subjective reports are highly valued because they provide qualitative and quantitative information about the characteristics of central and peripheral pharmacodynamic effects as well as safety and tolerability. However, self-administration procedures directly examine the behavior of interest -that is, drug taking. The present paper 1) reviews the most commonly used human self-administration procedures, 2) discusses the concordance of subjective reports and selfadministration within the context of medications development for substance use disorders, focusing primarily on illustrative examples from development efforts with opioid and cocaine dependence, and 3) explores the utility of applying self-administration procedures to assess the abuse liability of novel compounds, including "abuse deterrent" formulations (ADFs). The review will focus on opioid and cocaine dependence because a rich database from both clinical laboratory and clinical trial research exists for these two drug classes. The data reviewed suggest that drug-induced changes in self-administration and subjective effects are not always concordant. Therefore, assessment of selfadministration in combination with subjective effects provides a more comprehensive picture that may have improved predictive validity for translating to the clinical setting.

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“…Based on previous work using continuous access to drug selfadministration (Deneau et al, 1969;Johanson et al, 1976;Bozarth and Wise, 1985;Wolffgramm, 1991), we and others have recently developed and begun to validate an animal model of the transition to compulsive drug use (Ahmed and Koob, 1998;Mantsch et al, 2001;Paterson and Markou, 2003;Roth and Carroll, 2004;Vanderschuren and Everitt, 2004;Liu et al, 2005). Differential access to intravenous i.v.…”

Section: Introductionmentioning

confidence: 99%

Dissociation of Psychomotor Sensitization from Compulsive Cocaine Consumption

Ahmed¹,

Cador²

2005

Neuropsychopharmacol

146

143

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The transition from drug use to drug addiction is associated with a process of escalation, whereby drug use becomes excessive and difficult to control. Several mechanisms have been advanced to explain escalating patterns of drug use as opposed to nonescalating patterns. Although current evidence favors hedonic tolerance, there remains some dispute about the contribution of behavioral sensitization to cocaine intake escalation. Here, we concurrently assessed the ability of cocaine to induce psychomotor sensitization and drug-seeking behavior in animals with 1-h (short access or ShA) vs 6-h (long access or LgA) access to intravenous (i.v.) cocaine selfadministration. As expected, cocaine intake by LgA rats escalated over time and became excessive compared to cocaine intake by ShA rats, which remained low and stable. Despite escalated levels of cocaine consumption, however, LgA rats were not more sensitized to cocaine than ShA rats. The dose-effect function for cocaine-induced locomotion (0.125-1 mg, i.v.) was shifted to the left in LgA rats by the same amount as in ShA rats after cocaine self-administration. In contrast, LgA rats were much more responsive than ShA rats to the motivational effects of cocaine, as measured by the ability of i.v. cocaine to reinstate extinguished drug-seeking behavior. This study demonstrates a dissociation of psychomotor sensitization from the change in motivation underlying the transition to compulsive cocaine consumption, and therefore suggests that responsiveness to the motivational effects of the drug, not psychomotor sensitization, would represent a specific behavioral marker of the transition to and maintenance of compulsive cocaine use.

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Self-administration of psychoactive substances by the monkey

Cited by 775 publications

References 7 publications

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

Supply of a Nondrug Substitute Reduces Escalated Heroin Consumption

The role of human drug self-administration procedures in the development of medications

Dissociation of Psychomotor Sensitization from Compulsive Cocaine Consumption

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