Endocannabinoid signalling in reward and addiction

Parsons, Loren H.; Hurd, Yasmin L.

doi:10.1038/nrn4004

Cited by 399 publications

(377 citation statements)

References 214 publications

(282 reference statements)

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“…CB1 expression in WT mice was observed in brain areas that were selected for their involvement in cocaine-related behavioral responses (Parsons and Hurd, 2015). In general and as previously shown (Marsicano and Kuner, 2008), the levels of expression of CB1 in glutamatergic neurons were very low as compared with GABAergic neurons, which extensively expressed CB1 protein.…”

Section: Cb1 Expression In Key Brain Areasmentioning

confidence: 61%

Differential Control of Cocaine Self-Administration by GABAergic and Glutamatergic CB1 Cannabinoid Receptors

Martín‐García

Bourgoin

Cathala

et al. 2015

Neuropsychopharmacol

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The type 1 cannabinoid receptor (CB1) modulates numerous neurobehavioral processes and is therefore explored as a target for the treatment of several mental and neurological diseases. However, previous studies have investigated CB1 by targeting it globally, regardless of its two main neuronal localizations on glutamatergic and GABAergic neurons. In the context of cocaine addiction this lack of selectivity is critical since glutamatergic and GABAergic neuronal transmission is involved in different aspects of the disease. To determine whether CB1 exerts different control on cocaine seeking according to its two main neuronal localizations, we used mutant mice with deleted CB1 in cortical glutamatergic neurons (Glu-CB1) or in forebrain GABAergic neurons (GABA-CB1). In Glu-CB1, gene deletion concerns the dorsal telencephalon, including neocortex, paleocortex, archicortex, hippocampal formation and the cortical portions of the amygdala. In GABA-CB1, it concerns several cortical and non-cortical areas including the dorsal striatum, nucleus accumbens, thalamic, and hypothalamic nuclei. We tested complementary components of cocaine self-administration, separating the influence of primary and conditioned effects. Mechanisms underlying each phenotype were explored using in vivo microdialysis and ex vivo electrophysiology. We show that CB1 expression in forebrain GABAergic neurons controls mouse sensitivity to cocaine, while CB1 expression in cortical glutamatergic neurons controls associative learning processes. In accordance, in the nucleus accumbens, GABA-CB1 receptors control cocaine-induced dopamine release and Glu-CB1 receptors control AMPAR/NMDAR ratio; a marker of synaptic plasticity. Our findings demonstrate a critical distinction of the altered balance of Glu-CB1 and GABA-CB1 activity that could participate in the vulnerability to cocaine abuse and addiction. Moreover, these novel insights advance our understanding of CB1 neuropathophysiology.

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Section: Cb1 Expression In Key Brain Areasmentioning

confidence: 61%

Differential Control of Cocaine Self-Administration by GABAergic and Glutamatergic CB1 Cannabinoid Receptors

Martín‐García

Bourgoin

Cathala

et al. 2015

Neuropsychopharmacol

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“…THC has been shown to induce dopamine release in nucleus accumbens [25, 26], which is thought to underlie the rewarding effects of most drugs of abuse [27]. In addition, cannabinoids are shown to decrease GABA-mediated inhibitory transmission [28], modulate NMDA and AMPA receptor mediated excitatory transmission [29], and exert reinforcing effects via CB1-R activation in reward areas mediated by cholinergic and opioidergic systems [30]. …”

Section: Sex Differences In the Endocannabinoid Systemmentioning

confidence: 99%

Mechanisms Underlying Sex Differences in Cannabis Use

et al. 2017

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Purpose of the Review Cannabis is the most commonly used illicit substance worldwide. In recent decades, highly concentrated products have flooded the market, and prevalence rates have increased. Gender differences exist in cannabis use, as men have higher prevalence of both cannabis use and cannabis use disorder (CUD), while women progress more rapidly from first use to CUD. This paper reviews findings from preclinical and human studies examining the sex-specific neurobiological underpinnings of cannabis use and CUD, and associations with psychiatric symptoms. Recent Findings Sex differences exist in the endocannabinoid system, in cannabis exposure effects on brain structure and function, and in the co-occurrence of cannabis use with symptoms of anxiety, depression and schizophrenia. In female cannabis users, anxiety symptoms correlate with larger amygdala volume and social anxiety disorder symptoms correlate with CUD symptoms. Female cannabis users are reported to be especially vulnerable to earlier onset of schizophrenia, and mixed trends emerge in the correlation of depressive symptoms with cannabis exposure in females and males. Summary As prevalence of cannabis use may continue to increase given the shifting policy landscape regarding marijuana laws, understanding the neurobiological mechanisms of cannabis exposure in females and males is key. Examining these mechanisms may help inform future research on sex-specific pharmacological and behavioral interventions for women and men with high-risk cannabis use, comorbid psychiatric disease, and CUD.

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“…eCBs exert prominent modulatory influence on the extended amygdala and corticostriatal circuits, and stress exposure disrupts eCB-enriched regions that participate in emotional control [Serrano et al 2012; Dincheva et al 2015; Morena et al 2016]. Specifically, the relatively deficient eCB function is associated with increased anxiety and depression, and as such, impaired eCB activity may contribute to the negative affective states and increased stress responsivity that underlie negative reinforcement mechanisms driving alcohol drinking by dependent individuals and that contribute to alcohol relapse following periods of abstinence [Parsons & Hurd, 2015]. Pharmacologic and genetic manipulations (knockout or knock-in) of FAAH have been implicated in anxiolytic and anti-depressive behaviors [Bortolato et al 2007; Gunduz-Cinar et al 2013; Kathuria et al 2003; Moreira et al 2008; Carnevali et al 2015].…”

Section: Introductionmentioning

confidence: 99%

Blockade of alcohol escalation and “relapse” drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice

et al. 2017

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Background Anandamide (AEA)-dependent signaling is regulated by the catabolic enzyme fatty acid amide hydrolase (FAAH). Several lines of evidence have demonstrated that FAAH and AEA are involved in the behavioral effects of alcohol. Therefore, we investigated whether a selective FAAH inhibitor, URB597 (Cyclohexylcarbamic acid 3′-[aminocarbonyl]-[1,1′-biphenyl]-3-yl ester), altered alcohol intake in mice in a voluntary alcohol drinking model. Methods Mice, subjected to 3 weeks of chronic intermittent access (IA) in a two-bottle choice paradigm with 24-h access every other day, developed rapid escalation of alcohol intake and high preference. We evaluated the pharmacological effects of URB597 after both acute (1-day) withdrawal from chronic IA and 1-week withdrawal using the alcohol deprivation effect (ADE) model. AEA and N-acyl ethanolamide (NAE) abundances were determined after chronic IA, acute (1-day) or long-term (1 and 2 weeks) withdrawal in four brain regions. Results Acute pretreatment with URB597 reduced alcohol intake and preference after acute withdrawal. This effect was blocked by pretreatment with a selective type 1 cannabinoid receptor (CB1) antagonist, suggesting a CB1-mediated mechanism. Both single- and multiple- dosing regimens with an effective dose of URB597 prevented the ADE, with no tolerance development after the multi-dosing regimen. AEA and NAE levels were transiently increased in all brain regions measured after acute withdrawal, indicating that the endocannabinoid system is involved in acute alcohol withdrawal stress response. Conclusion FAAH inhibitors reduce alcohol escalation and “relapse” drinking in mice.

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Endocannabinoid signalling in reward and addiction

Cited by 399 publications

References 214 publications

Differential Control of Cocaine Self-Administration by GABAergic and Glutamatergic CB1 Cannabinoid Receptors

Differential Control of Cocaine Self-Administration by GABAergic and Glutamatergic CB1 Cannabinoid Receptors

Mechanisms Underlying Sex Differences in Cannabis Use

Blockade of alcohol escalation and “relapse” drinking by pharmacological FAAH inhibition in male and female C57BL/6J mice

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