Endocannabinoids regulate cocaine-associated memory through brain AEA–CB1R signalling activation

• DOI: 10.1016/j.molmet.2022.101597
• Publication Date: 2022-09-09T13:56:30Z
• Authors: Hongchun Li; Rong Chen; Yuanyi Zhou; Haichuan Wang; Luqiang Sun; Zhen Yang; Lin Bai; Jie Zhang
• Keywords: Anandamide; Signalling

Contextual drug-associated memory precipitates craving and relapse in substance users, the risk of is a major challenge treatment use disorders. Thus, understanding neurobiological underpinnings how this association formed maintained will inform future advances drug addiction. Brain endocannabinoids (eCBs) signalling has been associated with drug-induced neuroadaptations, but role lipases that mediate small lipid ligand biosynthesis metabolism regulating not examined. Here, we explored manipulation lipase fatty acid amide hydrolase (FAAH), which involved mediating level anandamide (AEA), affects cocaine-associated formation.We applied behavioural, pharmacological biochemical methods to detect formation, eCBs dorsal dentate gyrus (dDG), activity related enzymes. We further examined roles abnormal FAAH AEA-CB1R regulation formation granule neuron dendritic structure alterations dDG through Western blotting, electron microscopy immunofluorescence.In present study, found cocaine induced decrease increased AEA. A high AEA activated cannabinoid type 1 receptors (CB1Rs) triggered CB1R activation remodelling, these effects were reversed by blockade CB1Rs brain. Furthermore, inhibition markedly levels promoted activation.Together, our findings demonstrate influences alteration play key formation. Manipulation production may serve as potential therapeutic strategy for addiction prevention.