Repeated episodes of heroin cause enduring alterations of circadian activity in protracted abstinence.

Luis Stinus, Martine Cador, Stephanie Caille
Brain Sciences. 2012-09-20; 2(3): 421-433
DOI: 10.3390/brainsci2030421

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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.

DOI: 10.3390/brainsci2030421
PMCID: PMC4061796
PMID: 24961201

Auteurs Bordeaux Neurocampus