REDUCTION OF VOLUNTARY ETHANOL INTAKE IN ETHANOL-PREFERRING sP RATS BY THE CANNABINOID ANTAGONIST SR-141716

Colombo, Giancarlo; Agabio, Roberta; Fà, Mauro; Guano, Lorenza; Loche, Antonella; Reali, Roberta; Gessa, G L

doi:10.1093/oxfordjournals.alcalc.a008368

Cited by 214 publications

(163 citation statements)

References 9 publications

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“…This result is in line with previous studies showing reduced voluntary alcohol intake or operant self-administration in rats by SR 141716A (Arnone et al, 1997;Colombo et al, 1998b;Rodriguez et al, 1999). Consistently with these, CB1 knockout mice have shown greatly reduced ethanol consumption and preference (Hungund et al, 2003;Wang et al, 2003;Naassila et al, 2004).…”

Section: Systemic and Pfc Injections Of Sr141716a Reduce Ethanol Selfsupporting

confidence: 93%

“…Studies using blockade (Arnone et al, 1997;Rodriguez et al, 1999;Colombo et al, 1998b) or genetic inactivation of CB1 receptors (Hungund et al, 2003;Wang et al, 2003;Naassila et al, 2004) imply endocannabinoid signaling in regulation of ethanol self-administration. Brain expression profiling further points to the possibility that dysregulated expression of endocannabinoid genes, and signal transduction genes under their control, could contribute to high alcohol preference (Rimondini et al, 2002;Arlinde et al, 2004;Derkinderen et al, 2001).…”

Section: Differences In Endocannabinoid Transmission Between Aa and Amentioning

confidence: 99%

“…Endocannabinoid signaling has recently been shown to regulate various aspects of alcohol-seeking behavior (Hungund et al, 2003;Wang et al, 2003;Poncelet et al, 2003;Houchi et al, 2005;Colombo et al, 1998b;Rodriguez et al, 1999). The endocannabinoids, that is, arachidonyl ethanolamide (anandamide (AEA)) and arachidonyl glycerol (1-AG, 2-AG), are produced postsynaptically upon neuronal depolarization through hydrolysis of membrane lipids by N-acyl phosphatidylethanolamide-selective phospholipase D (NAPE-PLD).…”

Section: Introductionmentioning

confidence: 99%

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Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Hansson

Bermúdez‐Silva²,

Malinen

et al. 2006

Neuropsychopharmacol

149

155

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Endocannabinoid signaling has recently been implicated in ethanol-seeking behavior. We analyzed the expression of endocannabinoidrelated genes in key brain regions of reward and dependence, and compared them between the alcohol-preferring AA (Alko Alcohol) and nonpreferring ANA (Alko Non-Alcohol) rat lines. A decreased expression of fatty acid amidohydrolase (FAAH), the main endocannabinoid-degrading enzyme, was found in prefrontal cortex (PFC) of AA rats, and was accompanied by decreased enzyme activity in this region. Binding of the endocannabinoid-cannabinoid 1 (CB1) receptor ligand 3 [H]SR141716A, and [35S]GTPgS incorporation stimulated by the CB1 agonist WIN 55,212-2 were downregulated in the same area. Together, this suggests an overactive endocannabinoid transmission in the PFC of AA animals, and a compensatory downregulation of CB1 signaling. The functional role of impaired FAAH function for alcohol self-administration was validated in two independent ways. The CB1 antagonist SR141716A potently and dose-dependently suppressed self-administration in AA rats when given systemically, or locally into the PFC, but not in the striatum. Conversely, intra-PFC injections of the competitive FAAH inhibitor URB597 increased ethanol self-administration in nonselected Wistar rats. These results show for the first time that impaired FAAH function may confer a phenotype of high voluntary alcohol intake, and point to a FAAH both as a potential susceptibility factor and a therapeutic target.

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Section: Systemic and Pfc Injections Of Sr141716a Reduce Ethanol Selfsupporting

confidence: 93%

Section: Differences In Endocannabinoid Transmission Between Aa and Amentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Hansson

Bermúdez‐Silva²,

Malinen

et al. 2006

Neuropsychopharmacol

149

155

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“…The decreased rewarding effects of ethanol in CB 1 À/À mice might therefore be related to alteration of ethanol-induced dopamine release via CB 1 receptors in the mesocorticolimbic reward pathway. Recent observations have shown that the endogenous cannabinoid system facilitates the perception or the effects of positive reinforcers such as electrical brain stimulation (DerocheGamonet et al, 2001) and drugs of abuse (Chaperon et al, 1998;Colombo et al, 1998). The lack of morphine selfadministration in CB1 À/À mice was also associated with the inability of morphine to stimulate dopamine release in the nucleus accumbens (Mascia et al, 1999), as observed for ethanol (Hungund et al, 2003).…”

Section: Discussionmentioning

confidence: 92%

“…Thus, studies have shown that the CB 1 receptor antagonist SR141716A reduces alcohol intake (Arnone et al, 1997;Colombo et al, 1998;Rodriguez de Fonseca et al, 1999) and the motivation to consume alcohol in a progressive ratio paradigm in rats, while a CB 1 receptor agonist increased the motivation to consume alcohol alcohol in a progressive ratio paradigm . In addition, ethanol (0.5-2.0 g/kg) has been shown to decrease operant responding to a greater extent in CB 1 À/À mice than in wild-type mice, suggesting a possible role of CB 1 receptor in the rate disruptive effects of ethanol (Baskfield et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

Houchi

Babovic

Pierrefiche

et al. 2004

Neuropsychopharmacol

173

145

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Cannabinoids and ethanol activate the same reward pathways, and recent advances in the understanding of the neurobiological basis of alcoholism suggest that the CB 1 receptor system may play a key role in the reinforcing effects of ethanol and in modulating ethanol intake. In the present study, male CB 1 receptors knockout mice generated on a CD1 background displayed decreased ethanol-induced conditioned place preference (CPP) compared to wild-type (CB 1 þ / þ ) mice. Ethanol (0.5, 1.0, 1.5, and 2.0 g/kg) induced significant CPP in CB 1 þ / þ mice at all doses tested, whereas it induced significant CPP only at the highest dose of ethanol (2.0 g/kg) in CB 1 À/À mice.However, there was no genotypic difference in cocaine (20 mg/kg)-induced CPP. There was also no genotypic difference, neither in cocaine (10-50 mg/kg) nor in D-amphetamine (1.2-5 mg/kg)-induced locomotor effects. In addition, mutant and wild-type mice did not differ in sensitivity to the anxiolytic effects of ethanol (1.5 g/kg) when tested using the elevated plus maze. Interestingly, this decrease in ethanol efficacy to induce CPP in CB 1 À/À mice was correlated with an increase in D2/D3 receptors, as determined by [ 3 H]raclopride binding, whereas there was no difference in D1-like receptors, as determined by [ 3 H]SCH23390 binding, measured in the striatum from drug-naïve mice. This increase in D2/D3 binding sites observed in CB 1 knockout mice was associated with an altered locomotor response to the D2/D3 agonist quinpirole (low doses 0.02-0.1 mg/kg) but not to an alteration of quinpirole (0.1-1.0 mg/kg)-induced CPP compared to wild-type mice. Altogether, the present results indicate that lifelong deletion of CB 1 receptors reduced ethanol-induced CPP and that these reduced rewarding effects of ethanol are correlated to an overexpression of striatal dopamine D2 receptors.

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The Incentive Salience of Alcohol

Hutchison¹,

Haughey²,

Niculescu³

et al. 2008

Arch Gen Psychiatry

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Context The gene that codes for cannabinoid receptor 1 (CNR1) represents an important target for investigations designed to elucidate individual differences in the etiology of alcohol dependence. Objective To achieve a better understanding of the role of the CNR1 gene in the etiology and treatment of alcohol dependence. Design The present investigation spans multiple levels of analysis, including receptor binding in postmortem brain tissue, neuroimaging, human laboratory models, and analyses of treatment outcome data. Results Findings indicate that the C allele of rs2023239 is associated with greater CB1 binding in the prefrontal cortex, greater alcohol cue–elicited brain activation in the midbrain and prefrontal cortex, greater subjective reward when consuming alcohol, and more positive outcomes after treatment with a medication that targets the mesocorticolimbic neurocircuitry. In addition, there were strong correlations between cue-elicited brain activation and alcohol consumption measures in individuals with the C allele. Conclusion Individuals with the C allele may be more susceptible to changes in the mesocorticolimbic neurocircuitry that is involved in the attribution of incentive salience after repeated exposure to alcohol.

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REDUCTION OF VOLUNTARY ETHANOL INTAKE IN ETHANOL-PREFERRING sP RATS BY THE CANNABINOID ANTAGONIST SR-141716

Cited by 214 publications

References 9 publications

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

The Incentive Salience of Alcohol

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