Brain activity of anandamide: a rewarding bliss?

Abstract

Anandamide is a lipid mediator that acts as an endogenous ligand of CB1 receptors. These receptors are also the primary molecular target responsible for the pharmacological effects of Δ9-tetrahydrocannabinol, the psychoactive ingredient in Cannabis sativa. Several studies demonstrate that anandamide exerts an overall modulatory effect on the brain reward circuitry. Several reports suggest its involvement in the addiction-producing actions of other abused drugs, and it can also act as a behavioral reinforcer in animal models of drug abuse. Importantly, all these effects of anandamide appear to be potentiated by pharmacological inhibition of its metabolic degradation. Enhanced brain levels of anandamide after treatment with inhibitors of fatty acid amide hydrolase, the main enzyme responsible for its degradation, seem to affect the rewarding and reinforcing actions of many drugs of abuse. In this review, we will provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of anandamide, with a particular emphasis on its motivational/reinforcing properties. We will also discuss how modulation of anandamide levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmaco-therapeutic tools for the treatment of substance use disorders.

Effect of acute physical exercise on motor sequence memory

“…Because of such joined relationship with performance and because the existing animal literature strongly supports that AEA promotes plasticity in both the hippocampus and the striatum 17 , 38 , 39 , we cannot rule out that increased AEA affected hippocampal and/or striatal function in our experiment, despite the absence of a simple linear relationship. Moreover, AEA is the strongest endogenous agonist of the CB1 system 40 , which itself has known neuroprotective effects 41 .…”

Cannabis, cannabinoid receptors, and endocannabinoid system: yesterday, today, and tomorrow

“…the authors provide an overview from a preclinical perspective of the current state of knowledge regarding the behavioral pharmacology of ANA, with a particular emphasis on its motivational/reinforcing properties. They also discuss how modulation of ANA levels through inhibition of enzymatic metabolic pathways could provide a basis for developing new pharmacotherapeutic tools for the treatment of substance use disorders [4].…”

Triple-knockout, synuclein-free mice display compromised lipid pattern

“…As to the additional role of DHA in the brain, its endogenously synthesised endocannabinoid-like metabolite, N-docosahexaenoylethanolamine (synaptamide) has emerged as a potent mediator of neurotrophic and neuroprotective effects of DHA [83]. It is interesting that N-arachidonylethanolamine (anandamide) synthesised from ARA, being a structural analogue of synaptamide, possesses distinctive neuro-bioactivity modulating the brain reward circuitry and neuroin ammation [97].…”