CB1 Receptor Blockade Decreases Ethanol Intake and Associated Neurochemical Changes in Fawn‐Hooded Rats

Femenía, Teresa; García-Gutiérrez, María Salud; Manzanares, Jorge

doi:10.1111/j.1530-0277.2009.01074.x

Cited by 44 publications

(24 citation statements)

References 96 publications

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“…In Sardinian ethanol-preferring rats selected for high ethanol consumption (sP), systemic SR141716A treatment decreased voluntary consumption of 10% ethanol under limited and continuous access conditions (Colombo et al, 1998; Serra et al, 2001). Likewise, treatment with the CB 1 inverse agonists AM251 and SR147778 reduced ethanol consumption in both Fawn Hooded (Femenia et al, 2010) and Wistar (Lallemand and De Witte, 2006) rats chronically exposed to ethanol vapor. These results demonstrate that disruption of CB 1 signaling in mice and rats causes a robust and highly reproducible reduction in voluntary ethanol consumption.…”

Section: Voluntary Ethanol Drinkingmentioning

confidence: 99%

“…Pharmacological blockade of CB 1 using SR141716A prevents ethanol-stimulated dopamine release in the NAc of C57Bl6 wild-type but not CB 1 KO mice (Hungund et al, 2003). Treatment with AM251, another CB 1 inverse agonist, blocked ethanol-stimulated dopamine release in the NAc of ethanol-preferring Fawn Hooded rats (Femenia et al, 2010). Systemic treatment with SR141716A blocked sub-second dopamine increases in the NAc of Wistar rats subjected to in vivo voltammetry (Cheer et al, 2007).…”

Section: Ethanol-stimulated Dopamine Releasementioning

confidence: 99%

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Roles for the endocannabinoid system in ethanol-motivated behavior

Henderson-Redmond

Guindon

Morgan

2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Alcohol use disorder represents a significant human health problem that leads to substantial loss of human life and financial cost to society. Currently available treatment options do not adequately address this human health problem, and thus, additional therapies are desperately needed. The endocannabinoid system has been shown, using animal models, to modulate ethanol-motivated behavior, and it has also been demonstrated that chronic ethanol exposure can have potentially long-lasting effects on the endocannabinoid system. For example, chronic exposure to ethanol, in either cell culture or preclinical rodent models, causes an increase in endocannabinoid levels that results in down-regulation of the cannabinoid receptor 1 (CB1) and uncoupling of this receptor from downstream G protein signaling pathways. Using positron emission tomography (PET), similar down-regulation of CB1 has been noted in multiple regions of the brain in human alcoholic patients. In rodents, treatment with the CB1 inverse agonist SR141716A (Rimonabant), or genetic deletion of CB1 leads to a reduction in voluntary ethanol drinking, ethanol-stimulated dopamine release in the nucleus accumbens, operant self-administration of ethanol, sensitization to the locomotor effects of ethanol, and reinstatement/relapse of ethanol-motivated behavior. Although the clinical utility of Rimonabant or other antagonists/inverse agonists for CB1 is limited due to negative neuropsychiatric side effects, negative allosteric modulators of CB1 and inhibitors of endocannabinoid catabolism represent therapeutic targets worthy of additional examination.

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Section: Voluntary Ethanol Drinkingmentioning

confidence: 99%

Section: Ethanol-stimulated Dopamine Releasementioning

confidence: 99%

Roles for the endocannabinoid system in ethanol-motivated behavior

Henderson-Redmond

Guindon

Morgan

2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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“…These lines like their progenitors consume > 5 g/kg/day of ethanol and display a clear ethanol (11% or 10%) preference over water. The inbred Fawn Hooded rat, whether from a vendor in the United States or France, consumes ~4 g/kg/day of ethanol with a modest preference for 10% ethanol over water (Overstreet, Rezvani, Cowen, Chen, & Lawrence, 2006; Femenia, García-Gutiérrez, & Manzanares, 2010, respectively). In addition, some rat lines selectively bred for a different behavioral phenotype display modest to relatively high ethanol intakes per day.…”

Section: Introductionmentioning

confidence: 99%

Scheduled access alcohol drinking by alcohol-preferring (P) and high-alcohol-drinking (HAD) rats: Modeling adolescent and adult binge-like drinking

Bell

Rodd

Engleman

et al. 2014

Alcohol

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Binge alcohol drinking continues to be a public health concern among today’s youth and young adults. Moreover, an early onset of alcohol use, which usually takes the form of binge drinking, is associated with a greater risk for developing alcohol use disorders. Given this, it is important to examine this behavior in rat models of alcohol abuse and dependence. Toward that end, the objective of this article is to review findings on binge-like drinking by selectively bred alcohol-preferring (P) and high-alcohol-drinking (HAD) lines of rats. As reviewed elsewhere in this special issue, the P line meets all, and the HAD line meets most, of the proposed criteria for an animal model of alcoholism. One model of binge drinking is scheduled ethanol access during the dark cycle, which has been used by our laboratory for over 20 years. Our laboratory has also adopted a protocol involving the concurrent presentation of multiple ethanol concentrations. When this protocol is combined with limited access, ethanol intake is maximized yielding blood ethanol levels (BELs) in excess, sometimes greatly in excess, of 80 mg%. By extending these procedures to include multiple scheduled ethanol access sessions during the dark cycle for 5 consecutive days/week, P and HAD rats consume in 3 or 4 h as much as, if not more than, the amount usually consumed in a 24-h period. Under certain conditions, using the multiple scheduled access procedure, BELs exceeding 200 mg% can be achieved on a daily basis. An overview of findings from studies with other selectively bred, inbred, and outbred rats places these findings in the context of the existing literature. Overall, the findings support the use of P and HAD rats as animal models to study binge-like alcohol drinking and reveal that scheduled access procedures will significantly increase ethanol intake by other rat lines and strains as well.

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“…In particular, CB1 receptor manipulation is reported to affect ethanol-related behavior, and in fact CB1 antagonism decreases both voluntary ethanol intake and relapse to ethanol in several experimental models (Arnone et al, 1997; Colombo et al, 1998; Gallate and McGregor, 1999; Cippitelli et al, 2005; Economidou et al, 2006; Femenía et al, 2010; De Bruin et al, 2011; Getachew et al, 2011), suggesting that CB1 receptor blockade reduces the rewarding value of ethanol. In turn, chronic administration of ethanol is associated with increased concentrations of endocannabinoids, in accordance with a reduction in the activity of their removal mechanisms, and in CB1 receptor expression, thus affecting the system as a whole (Basavarajappa et al, 1998, 2000, 2003; Vinod et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats

Plescia¹,

Brancato²,

Marino³

et al. 2013

Front. Behav. Neurosci.

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Increasing evidence focuses on acetaldehyde (ACD) as the mediator of the rewarding and motivational properties of ethanol. Indeed, ACD stimulates dopamine release in the nucleus accumbens and it is self-administered under different conditions. Besides the dopaminergic transmission, the endocannabinoid system has been reported to play an important role in ethanol central effects, modulating primary alcohol rewarding effect, drug-seeking, and relapse behavior. Drug motivational properties are highlighted in operant paradigms which include response-contingent punishment, a behavioral equivalent of compulsive drug use despite adverse consequences. The aim of this study was thus to characterize ACD motivational and rewarding properties employing an operant-conflict paradigm in which rats, trained to lever press in order to get ACD solution (0.9%), undergo extinction, reinstatement and conflict sessions, according to a modified Geller–Seifter procedure. Furthermore, the role played by CB1 receptor system in modulating ACD-induced effects were investigated through the administration of CB1 receptor antagonist, AM281 (1 mg/kg, i.p.) during the extinction-, relapse-, and conflict-experiments. Our results indicate that ACD is able to induce and maintain an operant behavior, a high number of responses during extinction, an increase in the lever presses during the reinstatement phase, and a higher emission of punished responses during the conflict experiments, when compared to controls. The administration of AM281 is able to decrease ACD-seeking behavior during extinction, the number of lever presses during reinstatement and to strongly decrease the punished responses for ACD. Our data strengthen the idea that ACD may be responsible for the central effects of ethanol, and pinpoint at the CB1 system as one of the neural substrates underlying its addictive properties.

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CB1 Receptor Blockade Decreases Ethanol Intake and Associated Neurochemical Changes in Fawn‐Hooded Rats

Cited by 44 publications

References 96 publications

Roles for the endocannabinoid system in ethanol-motivated behavior

Roles for the endocannabinoid system in ethanol-motivated behavior

Scheduled access alcohol drinking by alcohol-preferring (P) and high-alcohol-drinking (HAD) rats: Modeling adolescent and adult binge-like drinking

Acetaldehyde as a drug of abuse: insight into AM281 administration on operant-conflict paradigm in rats

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