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Effects of training and withdrawal periods on heroin seeking induced by conditioned cue in an animal of model of relapse

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Abstract

Rationale

A high incidence of relapse can be triggered by exposure to conditioned cues previously associated with heroin. Extended access to drug and withdrawal are thought to affect the motivation for drug seeking.

Objectives

The present study evaluated how different periods of training to self-administer heroin and different periods of withdrawal affected drug seeking.

Materials and methods

Following 1 to 14 days of heroin self-administration, rats were left in the home environment for 1 or 14 days. Subsequently, rats were evaluated for extinction of nose poke during the first hour after being returned to the training apparatus. One hour later, a conditioned stimulus was presented to initiate cue-induced reinstatement.

Results

Extending the training period from 1 to 14 days caused an escalation of reinstatement of drug seeking induced by conditioned cues. Increasing the withdrawal period from 1 to 14 days produced a similar increase in reinstatement of drug seeking induced by cues. Reinstatement of drug seeking induced by cues was augmented by pretreatment with naltrexone (1, 5 mg/kg) 24 h prior to reinstatement on day 1, but not at 14 days of withdrawal from heroin self-administration.

Conclusions

These experiments demonstrate that increasing the duration of either heroin self-administration or the withdrawal periods from heroin self-administration augments the reinstatement induced by cues that were associated previously with heroin reinforcement. Additionally, we provide one of the first demonstrations that opiate withdrawal induces heroin seeking, as assessed in the reinstatement model.

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Acknowledgments

This work was supported by the National Basic Research Program of China (2003CB515404; 2009CB522008), Nature Science Foundation of China (30470554, 30670675) and Zhejiang (D2080515), and United States Public Health Service Grant #DA 015369 and sponsored by the Zhejiang Provincial High-level Innovative Health Talents.

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Authors and Affiliations

  1. Laboratory of Behavioral Neuroscience, Ningbo Addiction Research and Treatment Center, School of Medicine, Ningbo University, 42 Xibei Str., Ningbo, 315010, People’s Republic of China

    Wenhua Zhou, Fuqiang Zhang, Huifen Liu, Suien Tang, Miaojun Lai & Huaqiang Zhu

  2. Department of Neurosciences, Medical University of South Carolina, Charleston, SC, 29425, USA

    Wenhua Zhou & Peter W. Kalivas

Authors
  1. Wenhua Zhou
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  2. Fuqiang Zhang
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  3. Huifen Liu
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  4. Suien Tang
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  5. Miaojun Lai
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  6. Huaqiang Zhu
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  7. Peter W. Kalivas
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Correspondence to Wenhua Zhou.

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Zhou, W., Zhang, F., Liu, H. et al. Effects of training and withdrawal periods on heroin seeking induced by conditioned cue in an animal of model of relapse. Psychopharmacology 203, 677–684 (2009). https://doi.org/10.1007/s00213-008-1414-2

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  • DOI: https://doi.org/10.1007/s00213-008-1414-2

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