Endocannabinoid system and alcohol addiction: Pharmacological studies

Colombo, Giancarlo; Serra, Salvatore; Vacca, Giovanni; Carai, Mauro A.M.; Gessa, Gian Luigi

doi:10.1016/j.pbb.2005.01.022

Cited by 105 publications

(77 citation statements)

References 76 publications

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“…Furthermore, several reports suggest that blockade of the CB 1 -R decreases the intake of ethanol drinking in different animal models (Rodriguez de Fonseca et al, 1999;Lallemand et al, 2001Lallemand et al, , 2004Cippitelli et al, 2005;Colombo et al, 2005;Gessa et al, 2005;Economidou et al, 2006). The results of this study revealed that a 4-week consumption of ethanol increased CB 1 -R in CPu, VMN, and DG of the hippocampus.…”

Section: Discussionsupporting

confidence: 61%

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

Martínez

Manzanares

2006

Neuropsychopharmacol

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Preclinical and clinical studies suggest that the administration of the opioid antagonist naltrexone decreases the intake of ethanol. However, the neuroplastic adaptations in the brain associated to reduction of ethanol consumption remains to be elucidated. The aim of the study was to identify gene transcription alterations underlying the attenuation of voluntary ethanol intake by administration of naltrexone in rats. Increasing doses of naltrexone (0.7 mg/kg, 4 days and 1.4 mg/kg/day, 4 days) to rats with acquired high preferring ethanol consumption (43.5 g of ethanol/kg/day) decreased voluntary ethanol intake (50%). Voluntary ethanol consumption altered mopioid receptor function in the cingulate cortex, caudate-putamen (CPu), nucleus accumbens core (Acb C) and shell (Acb S), the expression of tyrosine hydroxylase (TH) in the ventral tegmental area and substantia nigra, proenkephalin (PENK) in the piriform cortex, olfactory tubercle, CPu, Acb C and Acb S, ventromedial nucleus (VMN) and paraventricular nucleus (PVN) of the hypothalamus, corticotropin releasing factor (CRF) in PVN, cannabinoid CB 1 receptor (CB 1 -R) in the CPu, hippocampus and VMN, and serotonin transporter (5-HTT) in the dorsal and median raphe nuclei. The reduction of ethanol intake induced by naltrexone was associated with a blockade or significant reduction of the changes produced by ethanol in the expression of these genes in key regions related to drug dependence. These results point to a role for the m-opioid receptor, TH, PENK, CRF, CB 1 -R, and 5-HTT genes in specific brain regions in the modulation of neuroadaptative mechanisms associated to the decrease of ethanol intake induced by naltrexone. INTRODUCTIONAlcoholism is a serious health, social, and familiar problem of difficult solution produced by the conjunction of different complex causes that reflect the interaction of genetic, environmental, socio-cultural, and personal factors (Saatcioglu et al, 2006). In general, the main objective in the treatment of alcohol dependence is the maintenance of the abstinence and the reduction of seeking behavior to avoid relapse. The development of alcohol dependence is a slow process produced by continuous and repeated consumption of ethanol that results specially damaging to subjects presenting high impulsivity, low self-esteem, and sensation-seeking behavior. The vulnerability to develop any kind of problems related to ethanol becomes even higher in patients with certain psychiatric disorders such as phobias, attention-deficit hyperactive disorder or affective disorders (anxiety, depression, or bipolar disorder) (Hines et al, 2005). The reinforcing actions of ethanol are enhanced in these situations facilitating the progression to ethanol dependence. It has been proposed that consumption of ethanol stimulates dopamine neurons by acting directly on the nucleus accumbens and by disinhibiting GABA mesencephalic neurons projecting into the dopamine tegmental area (Spanagel and Weiss, 1999;Kienast and Heinz, 2006). Alterations in dopamine neurons ...

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Section: Discussionsupporting

confidence: 61%

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

Martínez

Manzanares

2006

Neuropsychopharmacol

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“…Our data are in agreement with the results of recent pharmacological studies suggesting a role of brain endocannabinoid system in the neural circuitry regulating alcohol consumption and motivation to consume alcohol in different rodent models of excessive alcohol consumption. These results show that cannabinoid receptor agonists and antagonists stimulate and suppress, respectively, alcohol intake, alcohol selfadministration, and alcohol's motivational properties (see Colombo et al (2005) and, Maldonado et al (2006) for review). Hansson et al (2006) demonstrated a decrease of FAAH expression and activity in prefrontal cortex of alcohol-preferring AA rats compare with nonpreferring ANA rats.…”

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

121

102

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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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“…The endogenous cannabinoid system also appears to play an important role in the rewarding and reinforcing effects of alcohol (114,147). Pharmacological blockade or genetic ablation of CB1 receptors decrease operant self-administration of ethanol (148,149) and decrease voluntary consumption of ethanol in rats (150)(151)(152)(153)(154) and in mice (155)(156)(157)(158)(159).…”

Section: Alcoholmentioning

confidence: 99%

Endocannabinoid system involvement in brain reward processes related to drug abuse

Solinas

Yaşar

Goldberg

2007

Pharmacological Research

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Cannabis is the most commonly abused illegal drug in the world and its main psychoactive ingredient, delta-9-tetrahydrocannabinol (THC), produces rewarding effects in humans and non-human primates. Over the last several decades, an endogenous system comprised of cannabinoid receptors, endogenous ligands for these receptors and enzymes responsible for the synthesis and degradation of these endogenous cannabinoid ligands has been discovered and partly characterized. Experimental findings strongly suggest a major involvement of the endocannabinoid system in general brain reward functions and drug abuse. First, natural and synthetic cannabinoids and endocannabinoids can produce rewarding effects in humans and laboratory animals. Second, activation or blockade of the endogenous cannabinoid system has been shown to modulate the rewarding effects of noncannabinoid psychoactive drugs. Third, most abused drugs alter brain levels of endocannabinoids in the brain. In addition to reward functions, the endocannabinoid cannabinoid system appears to be involved in the ability of drugs and drug-related cues to reinstate drug-seeking behavior in animal models of relapse. Altogether, evidence points to the endocannadinoid system as a promising target for the development of medications for the treatment of drug abuse.

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Endocannabinoid system and alcohol addiction: Pharmacological studies

Cited by 105 publications

References 76 publications

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

Gene Transcription Alterations Associated with Decrease of Ethanol Intake Induced by Naltrexone in the Brain of Wistar Rats

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

Endocannabinoid system involvement in brain reward processes related to drug abuse

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