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. 2014 Dec 5;18(1):pyu025.
doi: 10.1093/ijnp/pyu025.

Chronic stimulation of the tone of endogenous anandamide reduces cue- and stress-induced relapse in rats

Claudia Chauvet  1 , Céline Nicolas  1 , Nathalie Thiriet  1 , Md Virginie Lardeux  1 , Andrea Duranti  1 , Marcello Solinas  2
Affiliations

Chronic stimulation of the tone of endogenous anandamide reduces cue- and stress-induced relapse in rats

Claudia Chauvet et al. Int J Neuropsychopharmacol. .

Erratum in

  • Erratum.
    [No authors listed] [No authors listed] Int J Neuropsychopharmacol. 2016 Apr 27;19(10):pyw031. doi: 10.1093/ijnp/pyw031. Int J Neuropsychopharmacol. 2016. PMID: 27207904 Free PMC article. No abstract available.

Abstract

Background: The endogenous cannabinoid system plays an important role in motivation, stress, and drug abuse. Pharmacologically, the endocannabinoid system can be stimulated by either agonists of CB1 receptors or inhibition of metabolic degradation of endogenous cannabinoids and consequent increases in their brain levels.

Methods: Here, we investigated whether chronic administration during a period of withdrawal of the fatty acid amide hydrolase inhibitor URB597, which increases anandamide levels, would decrease the risks of relapse to cocaine seeking. Rats were allowed to self-administer cocaine and then they underwent forced withdrawal for 28 days, during which they were treated with URB597 or vehicle. One day after the last injection, we investigated cocaine seeking in one 6h extinction session and relapse triggered by re-exposure to drug-associated cues or a pharmacological stressor.

Results: We found that administration of URB597 significantly decreases cocaine-seeking behavior and cue- and stress-induced relapse.

Conclusion: These results suggest that stimulation of the endocannabinoid system could be helpful to prevent relapse to cocaine addiction.

Keywords: FAAH; abstinence; addiction; chronic treatment; endocannabinoid; psychostimulants; relapse; stress.

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Figures

Figure 1.
Figure 1.
Experiment 1: effects of chronic URB597 treatment on cue-induced reinstatement. (A) Cocaine seeking in a 6h extinction session without cocaine-paired cues and (B) cue-induced reinstatement with reintroduction of the cues in rats administered daily with URB597 (0.3mg/kg i.p.) or vehicle during a 28-day period of abstinence. Note that for reasons of clarity inactive nose-poke responses in A are not shown. Three-way ANOVA followed by Student-Neuman-Keuls post hoc test, **p < 0.01 master cocaine different from yoked saline control, $$p < 0.01 URB-treated different from vehicle-treated control, ##p < 0.01 active different from inactive nose-pokes.
Figure 2.
Figure 2.
Experiment 2: effects of chronic URB597 treatment on stress-induced reinstatement. (A) Cocaine seeking in a 6h extinction session in the presence of cues previously paired with cocaine and (B) stress-induced reinstatement triggered by the pharmacological stressor yohimbine (1.25mg/kg i.p.) in rats administered daily with URB597 (0.3mg/kg i.p.) or vehicle during a 28-day period of abstinence. Two-way ANOVA followed by Student-Neuman-Keuls post hoc test: $p < 0.05 URB-treated different from vehicle-treated control, ##p < 0.01 active different from inactive nose-pokes.
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References

    1. Adamczyk P, Faron-Gorecka A, Kusmider M, Dziedzicka-Wasylewska M, Papp M, Filip M. (2012). Long-lasting increase in [(3)H]CP55,940 binding to CB1 receptors following cocaine self-administration and its withdrawal in rats. Brain Res 1451:34–43. - PubMed
    1. Adamczyk P, McCreary AC, Przegalinski E, Mierzejewski P, Bienkowski P, Filip M. (2009). The effects of fatty acid amide hydrolase inhibitors on maintenance of cocaine and food self-administration and on reinstatement of cocaine-seeking and food-taking behavior in rats. J Physiol Pharmacol 60:119–125. - PubMed
    1. Baker DA, Tran-Nguyen TL, Fuchs RA, Neisewander JL. (2001). Influence of individual differences and chronic fluoxetine treatment on cocaine-seeking behavior in rats. Psychopharmacology (Berl) 155:18–26. - PubMed
    1. Bortolato M, Mangieri RA, Fu J, Kim JH, Arguello O, Duranti A, Tontini A, Mor M, Tarzia G, Piomelli D. (2007). Antidepressant-like activity of the fatty acid amide hydrolase inhibitor URB597 in a rat model of chronic mild stress. Biol Psychiatry 62:1103–1110. - PubMed
    1. Bystrowska B, Smaga I, Frankowska M, Filip M. (2013). Changes in endocannabinoid and N-acylethanolamine levels in rat brain structures following cocaine self-administration and extinction training. Prog Neuropsychopharmacol Biol Psychiatry 50C:1–10. - PubMed

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