Relapse to cocaine- and heroin-seeking behavior mediated by dopamine D2 receptors is time-dependent and associated with behavioral sensitization

Taco J De Vries, Anton N M Schoffelmeer, Rob Binnekade, Halfdan S Raasø, Louk J M J Vanderschuren

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The sensitizing properties of drugs of abuse have been proposed to play an important role in the persistence of drug seeking behavior. We decided to evaluate the temporal relationship of dopamine D2 receptor-mediated drug seeking behavior and behavioral sensitization in animals with a history of cocaine and heroin self-administration. During early phases of withdrawal (<1 week), activation of dopamine D2 receptors with quinpirole resulted in robust, dose-dependent, reinstatement of (non-reinforced) responding in both cocaine- and heroin-trained rats. Cocaine and heroin seeking induced by quinpirole was associated with a dramatic enhancement of the psychomotor stimulant effects of the D2 agonist, indicating that sensitization to D2-mediated events had developed. During the late phase of withdrawal (>3 weeks), reinstatement of cocaine seeking by quinpirole was still apparent, but less robust. In heroin-trained rats, increases of responding were no longer observed. Interestingly, behavioral sensitization to quinpirole was still observed in cocaine-trained rats, but was absent in heroin-trained rats. Thus, it appears that dopamine D2 receptors have a time-dependent role in relapse to cocaine and heroin seeking which is strongly associated with a behaviorally sensitized state.

Original languageEnglish
Pages (from-to)18-26
Number of pages9
JournalNeuropsychopharmacology
Volume26
Issue number1
DOIs
Publication statusPublished - Jan 2002

Cite this

De Vries, Taco J ; Schoffelmeer, Anton N M ; Binnekade, Rob ; Raasø, Halfdan S ; Vanderschuren, Louk J M J. / Relapse to cocaine- and heroin-seeking behavior mediated by dopamine D2 receptors is time-dependent and associated with behavioral sensitization. In: Neuropsychopharmacology. 2002 ; Vol. 26, No. 1. pp. 18-26.
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abstract = "The sensitizing properties of drugs of abuse have been proposed to play an important role in the persistence of drug seeking behavior. We decided to evaluate the temporal relationship of dopamine D2 receptor-mediated drug seeking behavior and behavioral sensitization in animals with a history of cocaine and heroin self-administration. During early phases of withdrawal (<1 week), activation of dopamine D2 receptors with quinpirole resulted in robust, dose-dependent, reinstatement of (non-reinforced) responding in both cocaine- and heroin-trained rats. Cocaine and heroin seeking induced by quinpirole was associated with a dramatic enhancement of the psychomotor stimulant effects of the D2 agonist, indicating that sensitization to D2-mediated events had developed. During the late phase of withdrawal (>3 weeks), reinstatement of cocaine seeking by quinpirole was still apparent, but less robust. In heroin-trained rats, increases of responding were no longer observed. Interestingly, behavioral sensitization to quinpirole was still observed in cocaine-trained rats, but was absent in heroin-trained rats. Thus, it appears that dopamine D2 receptors have a time-dependent role in relapse to cocaine and heroin seeking which is strongly associated with a behaviorally sensitized state.",
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Relapse to cocaine- and heroin-seeking behavior mediated by dopamine D2 receptors is time-dependent and associated with behavioral sensitization. / De Vries, Taco J; Schoffelmeer, Anton N M; Binnekade, Rob; Raasø, Halfdan S; Vanderschuren, Louk J M J.

In: Neuropsychopharmacology, Vol. 26, No. 1, 01.2002, p. 18-26.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Relapse to cocaine- and heroin-seeking behavior mediated by dopamine D2 receptors is time-dependent and associated with behavioral sensitization

AU - De Vries, Taco J

AU - Schoffelmeer, Anton N M

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AU - Raasø, Halfdan S

AU - Vanderschuren, Louk J M J

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AB - The sensitizing properties of drugs of abuse have been proposed to play an important role in the persistence of drug seeking behavior. We decided to evaluate the temporal relationship of dopamine D2 receptor-mediated drug seeking behavior and behavioral sensitization in animals with a history of cocaine and heroin self-administration. During early phases of withdrawal (<1 week), activation of dopamine D2 receptors with quinpirole resulted in robust, dose-dependent, reinstatement of (non-reinforced) responding in both cocaine- and heroin-trained rats. Cocaine and heroin seeking induced by quinpirole was associated with a dramatic enhancement of the psychomotor stimulant effects of the D2 agonist, indicating that sensitization to D2-mediated events had developed. During the late phase of withdrawal (>3 weeks), reinstatement of cocaine seeking by quinpirole was still apparent, but less robust. In heroin-trained rats, increases of responding were no longer observed. Interestingly, behavioral sensitization to quinpirole was still observed in cocaine-trained rats, but was absent in heroin-trained rats. Thus, it appears that dopamine D2 receptors have a time-dependent role in relapse to cocaine and heroin seeking which is strongly associated with a behaviorally sensitized state.

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KW - Substance Withdrawal Syndrome

KW - Time Factors

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