CHRONIC ETHANOL CONSUMPTION REGULATES CANNABINOID CB 1 RECEPTOR GENE EXPRESSION IN SELECTED REGIONS OF RAT BRAIN

Aims: The aim of this study was to examine the effects of chronic ethanol consumption in cannabinoid CB1 receptor gene expression in Wistar rats. Methods: Rats were exposed to a bottle containing a solution of ethanol (10% v/v) and saccharin (0.25% w/v) for 52 days. At the end of this period, rats were killed by decapitation and cannabinoid CB1 receptor gene expression was measured by in situ hybridization histochemistry. Results: Our results indicated that chronic ethanol consumption reduced cannabinoid CB1 receptor gene expression in caudate-putamen (CPu) (24%), ventromedial nucleus of the hypothalamus (VMN) (43%), CA1 (27%) and CA2 (22%) fields of hippocampus and increased dentate gyrus (DG) (30%). Conclusions: These results reveal for the first time that prolonged exposure to ethanol produces marked alterations in cannabinoid CB1 receptor gene expression in selected regions of the rat brain, supporting an interaction between ethanol consumption and the endogenous cannabinoid receptor. Furthermore, these findings suggest that cannabinoid CB1 receptor may be considered as a new pharmacological target for treating ethanol dependence. Alcohol & Alcoholism Vol. 39, No. 2 © Medical Council on Alcohol 2004; all rights reserved *Author to whom correspondence should be addressed at: Servicio de Psiquiatría, Pabellón de Medicina Comunitaria, Hospital Universitario 12 de Octubre, Avda. de Córdoba s/n 28041 Madrid, Spain. Tel.: +34 91 390 8022; Fax: +34 91 390 8538; E-mail: jmanzanares6@terra.es

[1]  R. Gonzales,et al.  Ethanol increases extracellular dopamine concentration in the ventral striatum in C57BL/6 mice. , 2003, Alcoholism, clinical and experimental research.

[2]  J. García-Verdugo,et al.  Selective impairment of hippocampal neurogenesis by chronic alcoholism: Protective effects of an antioxidant , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[3]  T. Cooper,et al.  Chronic ethanol inhibits the anandamide transport and increases extracellular anandamide levels in cerebellar granule neurons. , 2003, European journal of pharmacology.

[4]  J. Manzanares,et al.  Behavioural and gene transcription alterations induced by spontaneous cannabinoid withdrawal in mice , 2003, Journal of neurochemistry.

[5]  C. Vadász,et al.  Cannabinoid CB1 receptor knockout mice exhibit markedly reduced voluntary alcohol consumption and lack alcohol‐induced dopamine release in the nucleus accumbens , 2003, Journal of neurochemistry.

[6]  R. Dingledine,et al.  Functional interactions between cannabinoid and metabotropic glutamate receptors in the central nervous system. , 2003, Current opinion in pharmacology.

[7]  Lei Wang,et al.  Endocannabinoid signaling via cannabinoid receptor 1 is involved in ethanol preference and its age-dependent decline in mice , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[8]  E. Nestler,et al.  Common Molecular and Cellular Substrates of Addiction and Memory , 2002, Neurobiology of Learning and Memory.

[9]  D. Parolaro,et al.  Chronic exposure to morphine, cocaine or ethanol in rats produced different effects in brain cannabinoid CB(1) receptor binding and mRNA levels. , 2002, Drug and alcohol dependence.

[10]  G. Gessa,et al.  Stimulation of voluntary ethanol intake by cannabinoid receptor agonists in ethanol-preferring sP rats , 2002, Psychopharmacology.

[11]  N. Jamshidi,et al.  Anandamide administration into the ventromedial hypothalamus stimulates appetite in rats , 2001, British journal of pharmacology.

[12]  L. Porrino,et al.  Effects of SR141716A on ethanol and sucrose self-administration. , 2001, Alcoholism, clinical and experimental research.

[13]  T. Cooper,et al.  Stimulation of cannabinoid receptor agonist 2-arachidonylglycerol by chronic ethanol and its modulation by specific neuromodulators in cerebellar granule neurons. , 2000, Biochimica et biophysica acta.

[14]  G. Koob,et al.  Cannabinoid receptor antagonist SR141716A decreases operant ethanol self administration in rats exposed to ethanol-vapor chambers. , 1999, Zhongguo yao li xue bao = Acta pharmacologica Sinica.

[15]  A. Ameri The effects of cannabinoids on the brain , 1999, Progress in Neurobiology.

[16]  J. Manzanares,et al.  Time-dependent differences of repeated administration with Delta9-tetrahydrocannabinol in proenkephalin and cannabinoid receptor gene expression and G-protein activation by mu-opioid and CB1-cannabinoid receptors in the caudate-putamen. , 1999, Brain research. Molecular brain research.

[17]  J. Manzanares,et al.  Differential basal proenkephalin gene expression in dorsal striatum and nucleus accumbens, and vulnerability to morphine self-administration in Fischer 344 and Lewis rats , 1999, Brain Research.

[18]  B. Basavarajappa,et al.  Down-regulation of cannabinoid receptor agonist-stimulated [ 35 S ]GTPγS binding in synaptic plasma membrane from chronic ethanol exposed mouse , 1999, Brain Research.

[19]  A. Rezvani,et al.  Distribution of opioid peptide gene expression in the limbic system of Fawn-Hooded (alcohol-preferring) and Wistar-Kyoto (alcohol-non-preferring) rats , 1998, Brain Research.

[20]  T. Cooper,et al.  Chronic ethanol administration down-regulates cannabinoid receptors in mouse brain synaptic plasma membrane , 1998, Brain Research.

[21]  G. Gessa,et al.  Reduction of voluntary ethanol intake in ethanol-preferring sP rats by the cannabinoid antagonist SR-141716. , 1998, Alcohol and alcoholism.

[22]  P. Soubrié,et al.  Selective inhibition of sucrose and ethanol intake by SR 141716, an antagonist of central cannabinoid (CB1) receptors , 1997, Psychopharmacology.

[23]  R. Handa,et al.  Alterations in the estrogen sensitivity of hypothalamic proenkephalin mRNA expression with age and prenatal exposure to alcohol. , 1997, Brain research. Molecular brain research.

[24]  M. Herkenham,et al.  Cannabinoid receptor localization in brain. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[25]  T. Bonner,et al.  Mesencephalic dopamine neurons regulate the expression of neuropeptide mRNAs in the rat forebrain. , 1986, Proceedings of the National Academy of Sciences of the United States of America.