Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization

Authors

  • Taco J. De Vries,

    1. Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands
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  • Anton N. M. Schoffelmeer,

    1. Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands
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  • Rob Binnekade,

    1. Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands
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  • Arie H. Mulder,

    1. Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands
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  • Louk J. M. J. Vanderschuren

    1. Research Institute Neurosciences Vrije Universiteit, Department of Pharmacology, Medical Faculty, Free University, Van der Boechorststraat 7, 1081 BT Amsterdam, the Netherlands
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Taco J. De Vries, as above. E-mail: tj.deÈvries.pharm@med.vu.nl

Abstract

The present study was designed to evaluate the relationship between reinstatement of drug-seeking behaviour following long-term extinction of intravenous (i.v.) drug self-administration (an animal model for craving) and long-term behavioural sensitization. Rats were allowed to self-administer heroin (50 μg/kg per inj., 14 daily sessions), cocaine (500 μg/kg per inj., 10 daily sessions) or saline. Following a 3-week extinction period, reinstatement tests were performed to evaluate priming effects of amphetamine, cocaine and heroin on non-reinforced drug-seeking behaviour. In addition, the occurrence of long-term behavioural sensitization in rats with a history of heroin or cocaine self-administration was determined. Heroin-seeking behaviour was reinstated by heroin (0.25 mg/kg), amphetamine (1.0 mg/kg) and cocaine (10 mg/kg). In addition, animals with a history of heroin self-administration displayed locomotor sensitization to both heroin and amphetamine. Cocaine-seeking behaviour was reinstated by cocaine and amphetamine, but not by heroin. Interestingly, locomotor sensitization to amphetamine, but not heroin, was observed in animals with a history of cocaine self-administration. In other words, the induction of drug-seeking behaviour following a prolonged drug-free period was found to be associated with the expression of long-term behavioural sensitization. These data provide experimental evidence for a role of behavioural sensitization in the incentive motivation underlying drug-seeking behaviour. If drug hyperresponsiveness would indeed be a crucial factor in drug-induced craving in human addicts, pharmacological readjustment of the neuroadaptations underlying drug sensitization may prevent relapse to drug use long after detoxification.

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