Chauvet Claudia, Nicolas Céline, Thiriet Nathalie, Lardeux Md Virginie, Duranti Andrea, Solinas Marcello
University of Poitiers, France (Drs Chauvet, Nicolas, Thiriet, Lardeux, and Solinas); INSERM, Experimental and Clinical Neurosciences Laboratory, Poitiers, FRANCE (Drs Nicolas, Thiriet, Lardeux, and Solinas); Dipartimento di Scienze Biomolecolari, Università degli Studi di Urbino "Carlo Bo," Urbino, Italy (Dr Duranti).
Int J Neuropsychopharmacol. 2014 Dec 5;18(1):pyu025. doi: 10.1093/ijnp/pyu025.
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.
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.
We found that administration of URB597 significantly decreases cocaine-seeking behavior and cue- and stress-induced relapse.
These results suggest that stimulation of the endocannabinoid system could be helpful to prevent relapse to cocaine addiction.
内源性大麻素系统在动机、应激和药物滥用中发挥着重要作用。从药理学角度来看，内源性大麻素系统可通过CB1受体激动剂或抑制内源性大麻素的代谢降解从而提高其在大脑中的水平来被激活。
在此，我们研究了在撤药期间长期给予脂肪酸酰胺水解酶抑制剂URB597（可提高花生四烯酸乙醇胺水平）是否会降低复吸可卡因的风险。让大鼠自行注射可卡因，然后强制戒断28天，在此期间给它们注射URB597或赋形剂。在最后一次注射后的一天，我们在一个6小时的消退期内研究了可卡因觅求行为，以及重新接触与药物相关的线索或药理应激源引发的复吸情况。
我们发现，给予URB597可显著降低可卡因觅求行为以及线索和应激诱导的复吸。
这些结果表明，刺激内源性大麻素系统可能有助于预防可卡因成瘾的复发。
