Behavioral Neurobiology of the Endocannabinoid System: 1 (Current Topics in Behavioral Neurosciences)

Behavioral Neurobiology of the Endocannabinoid System

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The endocannabinoid most researched in pain is palmitoylethanolamide. Palmitoylethanolamide is a fatty amine related to anandamide, but saturated and although initially it was thought that palmitoylethanolamide would bind to the CB1 and the CB2 receptor, later it was found that the most important receptors are the PPAR-alpha receptor , the TRPV receptor and the GPR55 receptor. Palmitoylethanolamide has been evaluated for its analgesic actions in a great variety of pain indications [63] and found to be safe and effective.

Basically these data are proof of concept for endocannabinoids and related fatty amines to be therapeutically useful analgesics; palmitoylethanolamide is available under the brand names Normast and PeaPure as nutraceuticals. Endocannabinoids are involved in placebo induced analgesia responses. Increased endocannabinoid signaling within the central nervous system promotes sleep-inducing effects.

Intercerebroventricular administration of anandamide in rats has been shown to decrease wakefulness and increase slow-wave sleep and REM sleep. Anandamide is an endogenous cannabinoid neurotransmitter that binds to cannabinoid receptors.

Endocannabinoid system - Wikipedia

In mice it was demonstrated that certain features of a runner's high depend on cannabinoid receptors. Pharmacological or genetic disruption of cannabinoid signaling via cannabinoid receptors prevents the analgesic and anxiety-reducing effects of running. Neuroscientists often utilize transgenic CB 1 knockout mice to discern novel roles for the endocannabinoid system.

While CB 1 knockout mice are healthy and live into adulthood, there are significant differences between CB 1 knockout and wild-type mice. When subjected to a high-fat diet, CB 1 knockout mice tend to be about sixty percent leaner and slightly less hungry than wildtype. The endocannabinoid system is by molecular phylogenetic distribution of apparently ancient lipids in the plant kingdom, indicative of biosynthetic plasticity and potential physiological roles of endocannabinoid-like lipids in plants, [77] and detection of arachidonic acid AA indicates chemotaxonomic connections between monophyletic groups with common ancestor dates to around million years ago silurian ; devonian.

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January Learn how and when to remove this template message. The Journal of Sexual Medicine. European Journal of Pharmacology. The traditional view that PA engages the monoaminergic and endorphinergic systems has been challenged by the discovery of the endocannabinoid system ECS , composed of endogenous lipids, their target receptors, and metabolic enzymes. Indeed, direct and indirect evidence suggests that the ECS might mediate some of the PA-triggered effects throughout the body. To our knowledge, the first experimental study aimed at investigating the influence of PA on ECS in humans was carried out in by Sparling and coworkers [63], who showed increased plasma AEA content after 45 min of moderate intensity exercise on a treadmill or cycle ergometer.

Since then, other human studies have shown increased blood concentrations of AEA A dependence of the increase of AEA concentration on exercise intensity has also been documented. Several experimental data support the hypothesis that ECS might, at least in part, explain PA effects on brain functions, because: Humans report a wide range of neurobiological rewards following moderate and intense aerobic activity, popularly referred to as the 'runner's high', which may function to encourage habitual aerobic exercise.

Circulating levels of endocannabinoids respond acutely to voluntary exercise, are altered in mice selectively bred for high voluntary wheel running, and differ between the sexes. How mobility and movement are at the center of human evolution. Issues, News, and Reviews Cell Death and Differentiation. British Journal of Pharmacology. Int J Obes Lond. Indeed, a fold increase in the potency of hypocretin-1 to activate the ERK signaling was observed when CB1 and HcrtR1 were co-expressed These data provide unambiguous identification of CB1-HcrtR1 heteromerization, which has a substantial functional impact.

The existence of a cross-talk between the hypocretinergic and endocannabinoid systems is strongly supported by their partially overlapping anatomical distribution and common role in several physiological and pathological processes. However, little is known about the mechanisms underlying this interaction.

CB1 is present in neurons of the enteric nervous system and in sensory terminals of vagal and spinal neurons in the gastrointestinal tract Massa et al. Activation of CB1 is shown to modulate nutrient processing, such as gastric secretion, gastric emptying, and intestinal motility. CB1 is shown to co-localize with the food intake inhibiting neuropeptide, corticotrophin-releasing hormone, in the paraventricular nucleus of the hypothalamus, and with the two orexigenic peptides, melanin-concentrating hormone in the lateral hypothalamus and with pre-pro-orexin in the ventromedial hypothalamus Inui, ; Horvath, The ECS works through many anorexigenic and orexigenic pathways where ghrelin, leptin, adiponectin, endogenous opioids, and corticotropin-releasing hormones are involved Viveros et al.

OX1—CB1 dimerization was suggested to strongly potentiate orexin receptor signaling, but a likely explanation for the signal potentiation is, instead, offered by the ability of OX1 receptor signaling to produce 2-arachidonoyl glycerol, a CB1 receptor ligand, and a subsequent co-signaling of the receptors Haj-Dahmane and Shen, ; Turunen et al. However, this does not preclude dimerization. Orexin receptor subtypes readily formed homo- and hetero di mers, as suggested by significant BRET signals. CB1 receptors formed homodimers, and they also heterodimerized with both orexin receptors.

However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations available for cannabinoid receptors. Activation of central CB1R The Open Pain Journal.

From Bench to Bedside 1st ed. A popular belief has been that endogenous endorphins mediate these beneficial effects. Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner's high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.

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Endocannabinoid system

In other projects Wikimedia Commons. This page was last edited on 7 November , at Visit our Beautiful Books page and find lovely books for kids, photography lovers and more. Other books in this series. Behavioral Pharmacology of Neuropeptides: Translational Neuropsychopharmacology Barbara J.

Neurogenesis and Neural Plasticity Catherine Belzung. Behavioral Neurogenetics John F. Neuroscience of Aggression Klaus A. Back cover copy The endocannabinoid signalling system is one of the key modulators of central nervous function. This volume provides timely and in-depth coverage of the roles of the endocannabinoid signalling system in the neurobiology of behavior. It is essential reading for any researcher with a background in neuroscience wanting to know more about the endocannabinoids.

The first section provides a comprehensive account of the component parts of the system the signalling molecules, synthetic and degradative enzymes and receptors , their location within the central nervous system and the endocannabinoids' roles in neural plasticity. This section also describes the toolboxes genetic and pharmacological used to study the system. The second section concentrates on endocannabinoid function in the control of normal physiological behaviors including a reference to the evolution of the system based on its operation in non-mammalian vertebrates.

The volume concludes by addressing the importance of the endocannabinoids in pathological behaviors including affective and cognitive disorders, neurodegenerative conditions, feeding and drug abuse.

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