Abstract
There is strong support for the role of the endocannabinoid system and the noncannabinoid lipid signaling molecules, N-acylethanolamines (NAEs), in cocaine reward and withdrawal. In the latest study, we investigated the changes in the levels of the above molecules and expression of cannabinoid receptors (CB1 and CB2) in several brain regions during cocaine-induced reinstatement in rats. By using intravenous cocaine self-administration and extinction procedures linked with yoked triad controls, we found that a priming dose of cocaine (10 mg/kg, i.p.) evoked an increase of the anadamide (AEA) level in the hippocampus and prefrontal cortex only in animals that had previously self-administered cocaine. In the same animals, the level of 2-arachidonoylglycerol (2-AG) increased in the hippocampus and nucleus accumbens. Moreover, the drug-induced relapse resulted in a potent increase in NAEs levels in the cortical areas and striatum and, at the same time, a decrease in the tissue levels of oleoylethanolamide (OEA) and palmitoylethanolamide (PEA) was noted in the nucleus accumbens, cerebellum, and/or hippocampus. At the level of cannabinoid receptors, a priming dose of cocaine evoked either upregulation of the CB1 and CB2 receptors in the prefrontal cortex and lateral septal nuclei or downregulation of the CB1 receptors in the ventral tegmental area. In the medial globus pallidus we observed the upregulation of the CB2 receptor only after yoked chronic cocaine treatment. Our findings support that in the rat brain, the endocannabinoid system and NAEs are involved in cocaine induced-reinstatement where these molecules changed in a region-specific manner and may represent brain molecular signatures for the development of new treatments for cocaine addiction.
Highlights
Cocaine use disorder continues to remain a major world health issue
Self-administration of cocaine induced both a potent decrease of the anandamide (AEA) levels in the cerebellum and in the 2-arachidonoylglycerol (2-AG) levels in the hippocampus and striatum with fewer cannabinoid CB1 receptors, while increased 2-AG levels were observed in the frontal cortex and cerebellum and were was linked with cocaine reward in rats [2,7]
For repeated measures for animals previously self-administered cocaine for tissue level of endocannabinoids and NAEs and expression of cannabinoid receptor experiments showing the significant effect of lever × session interaction (F(24,336) = 10.72; p < 0.001 and F(24,336) = 9.47; p < 0.001, respectively)
Summary
Cocaine use disorder continues to remain a major world health issue. According to the EuropeanMonitoring Centre for Drugs and Drug Addiction (EMCDDA) cocaine is the most commonly used illegal stimulant used in Europe [1] and a relapse in taking it belongs to the more difficult challenges undertaken during the treatment for both the patient and the physician. Cocaine use disorder continues to remain a major world health issue. The pathophysiology of this brain disorder still remains unclear. Self-administration of cocaine induced both a potent decrease of the anandamide (AEA) levels in the cerebellum and in the 2-arachidonoylglycerol (2-AG) levels in the hippocampus and striatum with fewer cannabinoid CB1 receptors, while increased 2-AG levels were observed in the frontal cortex and cerebellum and were was linked with cocaine reward in rats [2,7]. A cocaine-free period with extinction training resulted in a potent reduction of the endocannabinoid levels in the limbic and subcortical areas with the cannabinoid CB2 receptor downregulation [7]
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