Endocannabinoid system and drug addiction: new insights from mutant mice approaches

Maldonado, Rafaël; Robledo, Patricia; Berrendero, Fernando

doi:10.1016/j.conb.2013.02.004

Cited by 16 publications

(11 citation statements)

References 45 publications

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“…Preclinical animal studies have found an association between CB1 receptors and increases in impulsivity . Additionally, administering CB1 receptor antagonists, such as rimonabant, in animal models has been shown to reduce baseline impulsivity and self‐administration of several classes of substances . Further research in human models is warranted to investigate the role that the endocannabinoid system has on impulsivity and substance use as well as the potential to develop treatments targeting this system.…”

Section: Treatment Of Co‐occurring Impulsivity and Sudsmentioning

confidence: 99%

The neurobiology of impulsivity and substance use disorders: implications for treatment

Kozak

Lucatch

Lowe

et al. 2018

Annals of the New York Academy of Sciences

163

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Impulsivity is strongly associated with substance use disorders (SUDs). Our review discusses impulsivity as an underlying vulnerability marker for SUDs, and treatment of co‐occurring impulsivity in SUDs. Three factors should be considered for the complex relationship between impulsivity and a SUD: (1) the trait effect of impulsivity, centering on decreased cognitive and response inhibition, (2) the state effect resulting from either acute or chronic substance use on brain structure and function, and (3) the genetic and environmental factors (e.g., age and sex) may influence impulsive behavior associated with SUDs. Both subjective and objective measures are used to assess impulsivity. Together, treatment developments (pharmacological, behavioral, and neurophysiological) should consider these clinically relevant dimensions assessed by a variety of measures, which have implications for treatment matching in individuals with SUD. Despite its heterogeneity, impulsivity is a marker associated with SUDs and may be understood as an imbalance of bottom‐up and top‐down neural systems. Further investigation of these relationships may lead to more effective SUD treatments.

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Section: Treatment Of Co‐occurring Impulsivity and Sudsmentioning

confidence: 99%

The neurobiology of impulsivity and substance use disorders: implications for treatment

Kozak

Lucatch

Lowe

et al. 2018

Annals of the New York Academy of Sciences

163

View full text Add to dashboard Cite

show abstract

“…Most studies reported that the primary rewarding effects and the motivation to seek different drugs of abuse were attenuated by the inactivation of CB1 (Maldonado et al , 2006; Maldonado et al , 2013). Exercise has also shown to be a positive impact on the eCBs system.…”

Section: Underlying Neurobiological Mechanisms For the Sex-specifimentioning

confidence: 99%

Sex differences in drug addiction and response to exercise intervention: From human to animal studies

Zhou

Zhao

Zhou

et al. 2016

Frontiers in Neuroendocrinology

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Accumulated research supports the idea that exercise could be an option of potential prevention and treatment for drug addiction. During the past few years, there has been increased interest in investigating of sex differences in exercise and drug addiction. This demonstrates that sex-specific exercise intervention strategies may be important for preventing and treating drug addiction in men and women. However, little is known about how and why sex differences are found when doing exercise-induced interventions for drug addiction. In this review, we included both animal and human that pulled subjects from a varied age demographic, as well as neurobiological mechanisms that may highlight the sex-related differences in these potential to assess the impact of sex-specific roles in drug addiction and exercise therapies.

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“…Insulin signals converge here that underlie palatable food preference and food reward (Volkow et al, 2008;Kenny, 2011;Kullmann et al, 2015). The modulation of mesoaccumbal transmitter release and synaptic plasticity is also crucial in drug-induced reward and reinforcement of drug abuse -including that of cannabis -which are highly dependent on frontal cortical-mesoaccumbal endocannabinoid signaling (Robbe et al, 2003;Maldonado et al, 2013;Covey et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Hierarchical glucocorticoid-endocannabinoid interplay regulates the activation of the nucleus accumbens by insulin

Pinheiro

Lemos

Kaufmann

et al. 2016

Brain Research Bulletin

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Here we asked if insulin activation of the nucleus accumbens in vitro is reflected by an increase in (3)H-deoxyglucose ([(3)H]DG) uptake, thus subserving a new model to study molecular mechanisms of central insulin actions. Additionally, we investigated the dependence of this insulin effect on endocannabinoids and corticosteroids, two major culprits in insulin resistance. We found that in acute accumbal slices, insulin (3 and 300nM but not at 0.3nM) produced an increase in [(3)H]DG uptake. The synthetic cannabinoid agonist, WIN55212-2 (500nM) and the glucocorticoid dexamethasone (10μM), impaired insulin (300nM) action on [(3)H]DG uptake. The glucocorticoid receptor (GcR) antagonist, mifepristone (10μM) prevented dexamethasone from inhibiting insulin's action. Strikingly, this anti-insulin action of dexamethasone was also blocked by two CB1 cannabinoid receptor (CB1R) antagonists, O-2050 (500nM) and SR141716A (500nM), as well as by tetrahydrolipstatin (10μM), an inhibitor of diacylglycerol lipases-the enzymes responsible for the synthesis of the endocannabinoid, 2-arachidonoyl-glycerol (2-AG). On the other hand, the blockade of the post-synaptic 2-AG metabolizing enzymes, α,β-serine hydrolase domain 6/12 by WWL70 (1μM) also prevented the action of insulin, probably via increasing endogenous 2-AG tone. Additionally, an anti-insulin receptor (InsR) antibody immunoprecipitated CB1Rs from accumbal homogenates, indicating a physical complexing of CB1Rs with InsRs that supports their functional interaction. Altogether, insulin stimulates glucose uptake in the nucleus accumbens. Accumbal GcR activation triggers the synthesis of 2-AG that in turn binds to the known CB1R-InsR heteromer, thus impeding insulin signaling.

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Endocannabinoid system and drug addiction: new insights from mutant mice approaches

Cited by 16 publications

References 45 publications

The neurobiology of impulsivity and substance use disorders: implications for treatment

The neurobiology of impulsivity and substance use disorders: implications for treatment

Sex differences in drug addiction and response to exercise intervention: From human to animal studies

Hierarchical glucocorticoid-endocannabinoid interplay regulates the activation of the nucleus accumbens by insulin

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