Paradoxical effects of the endocannabinoid uptake inhibitor VDM11 on accumbal neural encoding of reward predictive cues

Oleson, Erik B.; Cheer, Joseph F.

doi:10.1002/syn.21587

Cited by 9 publications

(10 citation statements)

References 32 publications

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“…The effects observed with VDM11 and AM404 on nicotine reward/reinforcement, were further supported by Oleson and Cheer ( 119 ) using the intracranial brain stimulation paradigm. Elevating levels of anandamide using the anandamide uptake inhibitor VDM11 reduced NAc neural encoding of reward-predictive cues and attenuated reward seeking, defined as the time occurring between cue presentation and a reward-directed behavioral response ( 120 ).…”

Section: Similarities Between Faah Inhibitors and Endocannabinoid Uptmentioning

confidence: 53%

Role of the endogenous cannabinoid system in nicotine addiction: novel insights

et al. 2015

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Several lines of evidence have shown that the endogenous cannabinoids are implicated in several neuropsychiatric diseases. Notably, preclinical and human clinical studies have shown a pivotal role of the cannabinoid system in nicotine addiction. The CB1 receptor inverse agonist/antagonist rimonabant (also known as SR141716) was effective to decrease nicotine-taking and nicotine-seeking in rodents, as well as the elevation of dopamine induced by nicotine in brain reward area. Rimonabant has been shown to improve the ability of smokers to quit smoking in randomized clinical trials. However, rimonabant was removed from the market due to increased risk of psychiatric side-effects observed in humans. Recently, other components of the endogenous cannabinoid system have been explored. Here, we present the recent advances on the understanding of the role of the different components of the cannabinoid system on nicotine’s effects. Those recent findings suggest possible alternative ways of modulating the cannabinoid system that could have implication for nicotine dependence treatment.

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Section: Similarities Between Faah Inhibitors and Endocannabinoid Uptmentioning

confidence: 53%

Role of the endogenous cannabinoid system in nicotine addiction: novel insights

et al. 2015

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“…We suggest that our results are remarkably consistent with AM404 leading to reductions in release of 2‐AG during food habits—an effect mediated through subsequent reduced activity at CB1 receptors. Previously, an endocannabinoid transport inhibitor decreased neural encoding of reward predicting cues and decreased motivated operant behavior (Oleson & Cheer, ), which also could potentially be explained as a reduction in 2‐AG release (Oleson et al., ). However, we cannot rule out the possibility that this effect of AM404 may depend on reductions in the release of anandamide.…”

Section: Discussionmentioning

confidence: 99%

Bi‐directional modulation of food habit expression by the endocannabinoid system

Gianessi

Groman

Taylor

2019

Eur J of Neuroscience

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The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal‐directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co‐administration of an enzyme inhibitor that selectively increases the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.

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“…Moreover, increasing VTA levels of 2-AG by blocking its enzymatic degradation increased cue-evoked dopamine release and decreased response latency. Interestingly, increasing VTA levels of anandamide antagonized this effect, suggesting that anandamide impedes CB 1 receptor binding of 2-AG (Oleson and Cheer, 2012b). Because feeding and locomotion remained unaffected by the pharmacological treatments, this work indicates an important and selective role for the VTA eCB system in regulating cue-evoked NAc dopamine release and reward seeking.…”

Section: Section 3 Ecb Regulation Of Dopamine Signaling and Cue-dirementioning

confidence: 99%

Cannabinoid modulation of drug reward and the implications of marijuana legalization

2015

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Marijuana is the most popular illegal drug worldwide. Recent trends indicate that this may soon change; not due to decreased marijuana use, but to an amendment in marijuana’s illegal status. The cannabinoid type 1 (CB1) receptor mediates marijuana’s psychoactive and reinforcing properties. CB1 receptors are also part of the brain endocannabinoid (eCB) system and support numerous forms of learning and memory, including the conditioned reinforcing properties of cues predicting reward or punishment. This is accomplished via eCB-dependent alterations in mesolimbic dopamine function, which plays an obligatory role in reward learning and motivation. Presynaptic CB1 receptors control midbrain dopamine neuron activity and thereby shape phasic dopamine release in target regions, particularly the nucleus accumbens (NAc). By also regulating synaptic input to the NAc, CB1 receptors modulate NAc output onto downstream neurons of the basal ganglia motor circuit, and thereby support goal-directed behaviors. Abused drugs promote short- and long-term adaptations in eCB-regulation of mesolimbic dopamine function, and thereby hijack neural systems related to the pursuit of rewards to promote drug abuse. By pharmacologically targeting the CB1 receptors, marijuana has preferential access to this neuronal system and can potently alter eCB-dependent processing of reward-related stimuli. As marijuana legalization progresses, greater access to this drug should increase the utility of marijuana as a research tool to better understand the eCB system, which has the potential to advance cannabinoid-based treatments for drug addiction.

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Paradoxical effects of the endocannabinoid uptake inhibitor VDM11 on accumbal neural encoding of reward predictive cues

Cited by 9 publications

References 32 publications

Role of the endogenous cannabinoid system in nicotine addiction: novel insights

Role of the endogenous cannabinoid system in nicotine addiction: novel insights

Bi‐directional modulation of food habit expression by the endocannabinoid system

Cannabinoid modulation of drug reward and the implications of marijuana legalization

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