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Effects of anandamide administration on components of reward processing during free choice

aea reward motivation

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#1 Ruth

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Posted 21 July 2018 - 12:18 AM


Previous research has implicated the positive modulation of anandamide, an endocannabinoid neurotransmitter, on feeding behavior. Anandamide is particularly noteworthy as it acts as an endogenous ligand of the CB1 receptor, the same receptor that is activated by tetrahydrocannabinol, the primary psychoactive component in Cannabis sativa. Cannabis legalization in North America has presented with a need to study endocannabinoid agonistsandtheireffectsonbehavior.Muchhasyettobedeterminedintermsoftheroleoftheendocannabinoid system in decision-making scenarios. The research presented here tested the hypothesis that anandamide would augment motivation and reward processing via appetitive and consummatory measures during an operant, foraging task. A three-box design was used in order to provide the animals with a free choice, exploratory foraging environment. Discrimination, preference, and incentive contrast were analyzed as discrete measures of decision-making in the three-box paradigm. Anandamide administration (1 mg/kg) was found to significantly increase motivation for the optimal foraging outcome and alter basic processing of reward information involved in discrimination and relative valuation. The positive effects of anandamide on eating behavior and motivation have implications toward possible treatment modalities for patient populations presenting with disorders of motivation. These findings suggest the need for continued investigation of the endocannabinoid system as a central component of motivated behavior.
"It is almost impossible to discuss THC without also mentioning cannabidiol (CBD), another phytocannabinoid present in cannabis, though in comparatively lower amounts (Swift et al., 2013). Recently, CBD has been indicated to attenuate motivational dysfunction by elevating anandamide (N-arachidonoylethanolamine; AEA) levels and activation of the 5-HT1a receptor (Zlebnik and Cheer, 2016). More specifically, CBD may reduce depressive symptoms such as anhedonia and associated amotivation by simulating anandamide-dependent neurogenesis in the hippocampus of mice (Campos et al., 2013). Additionally, serum anandamide levels have been found to negatively correlate with anxiety in female patients with major depression (Hill et al., 2008). This series of evidence suggests anandamide may be a key compound involved in motivation (Zlebnik and Cheer, 2016). Anandamide is a neurotransmitter/neuromodulator that functions as an endogenous ligand of CB1 receptors. Synthesized via multiple pathways involving hydrolysis of phospholipid precursors, anandamide is a hydrophobic molecule which diffuses from the postsynaptic membrane to affect its presynaptic targets without the need for vesicular secretion (Freund et al., 2003). Anandamide functions as a partial agonist of the CB1 receptor, which is a g-protein coupled receptor most prevalent in the nucleus accumbens (NAcc), cerebellum, hippocampus, and prefrontal cortex (Howlett et al., 2002; Mahler et al., 2007; Solinas et al., 2008; Karimi et al., 2013). The distribution of CB1 receptors and anandamide's effect on them suggests that it is involved in the regulation of a large suite of motivated behaviors."

#2 Ruth

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Posted 21 July 2018 - 12:38 AM

Synthetic analogues of natural products
Macamides are natural products that a bear structural similarity to AEA. Wu et. al. (2013)
synthesized some synthetic analogues of macamides, unique series of non-polar, long-chain
fatty acid N-benzylamides obtained from the plant maca (Lepidium meyenii), which is
widely used as a food supplement. Of the analogues synthesized, they found out that only
five were active as FAAH inhibitors in sub-micromolar range with the most potent being
compound 45 with almost 100% inhibition. They evaluated three compounds in a pre
incubation time study and found out that two of the analogues were not reversible inhibitors
of FAAH whereas the third 45, the most potent, a carbamate structurally related to
macamides, was an irreversible inhibitor of FAAH.
Amides

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