Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice

Naassila, Mickaël; Pierrefiche, Olivier; Ledent, Catherine; Daoust, M.

doi:10.1016/j.neuropharm.2003.09.002

Cited by 144 publications

(162 citation statements)

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“…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). These studies have provided convincing support for the notion that the endocannabinoid system is involved in regulation of ethanol consumption.…”

Section: Systemic and Pfc Injections Of Sr141716a Reduce Ethanol Selfsupporting

confidence: 67%

“…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%

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Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Hansson

Bermúdez‐Silva²,

Malinen

et al. 2006

Neuropsychopharmacol

151

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: 67%

Section: Differences In Endocannabinoid Transmission Between Aa and Amentioning

confidence: 99%

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Hansson

Bermúdez‐Silva²,

Malinen

et al. 2006

Neuropsychopharmacol

151

155

View full text Add to dashboard Cite

show abstract

“…A similar downregulation of these receptors was observed after chronic treatment with the natural cannabinoid agonist ⌬ 9 -tetra-hydrocannabinol or with CP-55,940 (Rodríguez de Fonseca et al, 1994;Rubino et al, 1994;Breivogel et al, 2003). In studies with mice lacking the cannabinoid CB 1 receptor (CB 1 Ϫ/Ϫ ), a decrease in both voluntary EtOH intake and EtOH operant self-administration was found (Hungund et al, 2003;Naassila et al, 2004).…”

Section: Introductionmentioning

confidence: 62%

Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

López-Moreno

González-Cuevas²,

Fonseca³

et al. 2004

J. Neurosci.

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“…In recent years, a large body of evidence points to the endogenous cannabinoid CB 1 -R as a relevant target involved in the vulnerability and development of ethanol consumption (Hungund and Basavarajappa, 2000;Basavarajappa and Hungund, 2002;Hungund et al, 2003;Wang et al, 2003;Naassila et al, 2004;Ortiz et al, 2004a, b;Houchi et al, 2005;Manzanares et al, 2005). 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).…”

Section: Discussionmentioning

confidence: 99%

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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Decreased alcohol self-administration and increased alcohol sensitivity and withdrawal in CB1 receptor knockout mice

Cited by 144 publications

References 59 publications

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Genetic Impairment of Frontocortical Endocannabinoid Degradation and High Alcohol Preference

Long-Lasting Increase of Alcohol Relapse by the Cannabinoid Receptor Agonist WIN 55,212-2 during Alcohol Deprivation

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

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