Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice

Basavarajappa, Balapal S.; Yalamanchili, Ratnakumar; Cravatt, Benjamin F.; Cooper, Thomas B.; Hungund, Basalingappa L.

doi:10.1016/j.neuropharm.2005.12.005

Cited by 108 publications

(98 citation statements)

References 58 publications

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“…This is consistent with the observation that high-drinking C57BL/6 mice have lower levels of CB1-binding sites, but higher receptor affinity and coupling than low-drinking DBA/2 mice . Our results are also consistent with a recent study of FAAH null mutant mice (Basavarajappa et al, 2006), although their changes in ethanol intake and preference were sex-dependent, whereas we found similar results from both sexes. These inconsistencies may be due to differences in the genetic background of the mutant mice used in the two studies.…”

Section: Discussionsupporting

confidence: 93%

“…These inconsistencies may be due to differences in the genetic background of the mutant mice used in the two studies. The wild-type mice used by Basavarajappa et al (2006) displayed much higher alcohol consumption than our mice and this may have limited the ability of the mutation to further increase drinking. Because female mice have higher alcohol consumption than male mice, such a 'ceiling effect' may be more pronounced for females, which is consistent with the published data.…”

Section: Discussionmentioning

confidence: 84%

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Role of Endocannabinoids in Alcohol Consumption and Intoxication: Studies of Mice Lacking Fatty Acid Amide Hydrolase

Blednov¹,

Cravatt

Boehm

et al. 2006

Neuropsychopharmacol

123

103

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Endocannabinoid signaling plays the important role in regulation of ethanol intake. Fatty acid amide hydrolase (FAAH) is a key membrane protein for metabolism of endocannabinoids, including anandamide, and blockade of FAAH increases the level of anandamide in the brain. To determine if FAAH regulates ethanol consumption, we studied mutant mice with deletion of the FAAH gene. Null mutant mice showed higher preference for alcohol and voluntarily consumed more alcohol than wild-type littermates. There was no significant difference in consumption of sweet or bitter solutions. To determine the specificity of FAAH for ethanol intake, we studied additional ethanol-related behaviors. There were no differences between null mutant and wild-type mice in severity of ethanol-induced acute withdrawal, conditioned taste aversion to alcohol, conditioned place preference, or sensitivity to hypnotic effect of ethanol. However, null mutant mice showed shorter duration of loss of righting reflex induced by low doses of ethanol (3.2 and 3.4 g/kg) and faster recovery from motor incoordination induced by ethanol. All three behavioral phenotypes (increased preference for ethanol, decreased sensitivity to ethanol-induced sedation, and faster recovery from ethanol-induced motor incoordination) seen in mutant mice were reproduced in wild-type mice by injection of a specific inhibitor of FAAH activityFURB597. These data suggest that increased endocannabinoid signaling increased ethanol consumption owing to decreased acute ethanol intoxication.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 84%

Role of Endocannabinoids in Alcohol Consumption and Intoxication: Studies of Mice Lacking Fatty Acid Amide Hydrolase

Blednov¹,

Cravatt

Boehm

et al. 2006

Neuropsychopharmacol

123

103

View full text Add to dashboard Cite

show abstract

“…In the same study, FAAH activity and CB 1 signaling were both reduced in the same brain region of AA rats compared with their nonpreferring ANA counterparts, and microinjection of the FAAH inhibitor URB597 increased ethanol self-administration (Hansson et al, 2006). Analogous findings in female FAAH knockout mice are their increased voluntary ethanol intake and decreased alcohol sensitivity (Basavarajappa et al, 2006). These findings suggest that increased anandamide tone secondary to decreased FAAH activity in the prefrontal cortex may be causally linked to high alcohol preference.…”

mentioning

confidence: 82%

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

2006

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Section: Role Of the Faah In Alcohol-related Behaviormentioning

confidence: 99%

“…There are a limited number of studies that have investigated the role of FAAH in alcohol drinking behavior [55,64,92]. It was reported that the mice lacking FAAH gene on a mixed genetic background (B6/129SV/J) consume significantly more alcohol compared to their WT counterparts [92]. An increase in alcohol intake has been shown in mice following administration of the FAAH inhibitor URB597 as well as in genetically homogeneous B6 mice lacking FAAH gene [55,64] (Fig.…”

Section: Role Of the Faah In Alcohol-related Behaviormentioning

confidence: 99%

Role of the Endocannabinoid System in Alcohol-Related Behaviors

Hungund¹

2011

tonj

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Alcoholism is a psychiatric disorder characterized by impaired control over drinking, leading to tolerance, physical dependence, uncontrollable craving and relapse. The mechanism/s underlying this disorder is poorly understood at present. Ethanol (alcohol) effects are mediated through several signal transduction pathways involving many neurotransmitters and ion channels in various brain regions. There is a growing body of evidence now suggesting a critical role for the endocannabinoid (EC) system in alcohol-related behaviors. The EC system is comprised of endogenous cannabimimetic substances (endocannabinoids) and their receptors [cannabinoid (CB)] and the enzymes involved in the synthesis and degradation of the ECs. Recent studies have demonstrated that both the genetic and pharmacological manipulation of the EC system modulate the development of tolerance to and dependence on alcohol. The present article provides a review of the existing literature on the role of the EC system, and possible mechanisms and the therapeutic potential of the drugs targeted against this system in preventing alcohol addiction.

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Increased ethanol consumption and preference and decreased ethanol sensitivity in female FAAH knockout mice

Cited by 108 publications

References 58 publications

Role of Endocannabinoids in Alcohol Consumption and Intoxication: Studies of Mice Lacking Fatty Acid Amide Hydrolase

Role of Endocannabinoids in Alcohol Consumption and Intoxication: Studies of Mice Lacking Fatty Acid Amide Hydrolase

The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Role of the Endocannabinoid System in Alcohol-Related Behaviors

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