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Brain Sci. 2012, 2(3), 421-433; doi:10.3390/brainsci2030421
Article

Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence

1,2
, 1,2
 and 1,2,*
Received: 31 July 2012; in revised form: 4 September 2012 / Accepted: 11 September 2012 / Published: 20 September 2012
(This article belongs to the Special Issue Addiction and Neuroadaptation)
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Abstract: Opiate withdrawal is followed by a protracted abstinence syndrome consisting of craving and physiological changes. However, few studies have been dedicated to both the characterization and understanding of these long-term alterations in post-dependent subjects. The aim of the present study was to develop an opiate dependence model, which induces long-lasting behavioral changes in abstinent rats. Here, we first compared the effects of several protocols for the induction of opiate dependence (morphine pellets, repeated morphine or heroin injections) on the subsequent response to heroin challenges (0.25 mg/kg) at different time points during abstinence (3, 6, 9 and 18 weeks). In a second set of experiments, rats were exposed to increasing doses of heroin and subsequently monitored for general circadian activity up to 20 weeks of abstinence. Results show that heroin injections rather than the other methods of opiate administration have long-term consequences on rats’ sensitivity to heroin with its psychostimulant effects persisting up to 18 weeks of abstinence. Moreover, intermittent episodes of heroin dependence rather than a single exposure produce enduring alteration of the basal circadian activity both upon heroin cessation and protracted abstinence. Altogether, these findings suggest that the induction of heroin dependence through intermittent increasing heroin injections is the optimal method to model long-term behavioral alterations during protracted abstinence in rats. This animal model would be useful in further characterizing long-lasting changes in post-dependent subjects to help understand the prolonged vulnerability to relapse.
Keywords: opiate; dependence; protracted abstinence; circadian activity; rats opiate; dependence; protracted abstinence; circadian activity; rats
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Stinus, L.; Cador, M.; Caille, S. Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence. Brain Sci. 2012, 2, 421-433.

AMA Style

Stinus L, Cador M, Caille S. Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence. Brain Sciences. 2012; 2(3):421-433.

Chicago/Turabian Style

Stinus, Luis; Cador, Martine; Caille, Stephanie. 2012. "Repeated Episodes of Heroin Cause Enduring Alterations of Circadian Activity in Protracted Abstinence." Brain Sci. 2, no. 3: 421-433.



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