ReviewShort- and long-term plasticity of the endocannabinoid system in neuropsychiatric and neurological disorders
Section snippets
Introduction—“on demand” or “long-term” regulation of endocannabinoid levels
The regulation of the tissue concentrations of the endogenous agonists of cannabinoid receptors, or endocannabinoids, and the nature of the signal that they convey is strongly determined by their chemical nature. In fact, the two most studied endocannabinoids, anandamide and 2-arachidonoyl-glycerol (2-AG), are lipophilic compounds produced from the remodelling of membrane phospholipids, and as such are not stored into vesicles to be released following exocytosis. Instead, they are made “on
“On demand” or “long-term” activation of the EC system in stress and emotions
Increasing evidence is accumulating to suggest that endocannabinoid plasticity occurs following conditions of mild or strong stress in laboratory animals. In fact, if one looks at the pharmacological actions associated with stimulation of cannabinoid CB1 and CB2 receptors, they all fit very well with a possible general function of the endocannabinoid system as a “stress-recovery” mechanism. Two experimental conditions that resemble acute stressful stimuli are brief food deprivation and
“On demand” activation of the EC system in acute neurological conditions
Some acute pathological conditions of the CNS offer ideal examples of the “on demand” regulation of endocannabinoid biosynthesis [92]. In the hippocampus, glutamate-induced neuronal depolarisation and/or Gq/11-mediated intracellular Ca2+ mobilization cause excitotoxicity along with transient elevations of the levels of endocannabinoids, which can then be released and act retrogradely to inhibit glutamate release from principal neurons [19], thus dampening neuronal excitability [7], [21], [93],
Short- and long-term activation or impairment of the endocannabinoid system in chronic or degenerative neurological disorders
During neurodegenerative disorders, the “output” of the endocannabinoid system appears to become either permanently activated or impaired. The role of endocannabinoids and cannabinoid CB1 and CB2 receptors in these disorders, which are characterized by distinct aetiologies and progress, but present several common features, have been recently the subject of comprehensive reviews [122], [123]. There is increasing evidence that, in animal models of either Parkinson's disease (PD) (reserpine-,
Conclusions—new therapeutic avenues from the endocannabinoid system
From the several experimental studies reviewed in this article, the general scenario emerges of an endocannabinoid system undergoing profound changes in the central nervous system during most of the neurological and psychiatric disorders investigated to date. The protective function of an elevated endocannabinoid tone in some cases (e.g., in models of multiple sclerosis, epilepsy, neuropathic pain, head trauma, ALS) is supported by overwelming data obtained using biochemical, genetic and
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2019, Neurochemistry InternationalCitation Excerpt :As reported by several studies (Angelotti et al., 1993; Connelly et al., 2013; Kapur and Macdonald, 1996; Vithlani et al., 2011) and confirmed by our previous experiments (Eroli et al., 2018), activation of AC and cAMP synthesis enhances responses evoked by GABA. While the current sustained application of cannabinoid agonists may not mimic the pattern of repeated human self-administration of cannabinoids, it has been reported that, after experimental lesion to the nervous system, the level of endocannabinoids is persistently increased (up to 24 h; Garcia-Ovejero et al., 2009), a phenomenon suggested to occur also in other pathological conditions like neuroinflammation and neurodegeneration (Bisogno and Di Marzo, 2007). Furthermore, cannabinoid metabolites can linger for many hours or even days in humans with potential for sustained CB1 activity (Schlienz et al., 2018).
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