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Abstract:

The endocannabinoid (eCB) system is involved in the modulation of the reward system and participates in the reinforcing effects of different drugs of abuse, including alcohol. The most abundant receptor of the eCB system in the central nervous system is the CB1 receptor (CB1R), which is predominantly expressed in areas involved in drug addiction, such as the nucleus accumbens, the ventral tegmental area, the substantia nigra and the raphe nucleus. CB1R is expressed in early stages during development, and reaches maximum levels during early adolescence. In addition, cannabinoid receptor 2 has been found expressed also in the central nervous system at postsynaptic level. In order to analyze the participation of the eCB system on ethanol (EtOH) preference, mice were exposed to cannabinoid agonist WIN 55,212-2 (WIN) for 5 consecutive days during early adolescence. Anxiety tests were performed the day after WIN treatment withdrawal, and EtOH preference was measured throughout adolescence. Mice exposed to WIN during early adolescence exhibited a significant increase in EtOH intake and preference after treatment. Moreover, WIN exposure during early adolescence induced an anxiogenic effect. Morphometric analysis revealed higher dendritic ramifications and fewer dendritic spines in neurons of the substantia nigra pars compacta in WIN-treated mice. On the other hand, immunohistochemical analysis revealed an increase in the number of tryptophan hydroxylase-expressing neurons in the dorsal raphe nucleus but no differences were found in the ventral tegmental area or substantia nigra pars compacta for tyrosine hydroxylase-expressing neurons. These results demonstrate that exposure to WIN in early adolescence can affect neural development and induce alcohol preference and anxiety-like behavior during late adolescence. © 2018 Elsevier Ltd

Registro:

Documento: Artículo
Título:Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice
Autor:Frontera, J.L.; Gonzalez Pini, V.M.; Messore, F.L.; Brusco, A.
Filiación:Universidad de Buenos Aires, Facultad de Ciencias Exactas y Naturales, Departamento de Fisiología, Biología Molecular y Celular, Bs As, Argentina
CONICET- Universidad de Buenos Aires, Instituto de Biología Celular y Neurociencia (IBCN), Bs As, Argentina
Universidad de Buenos Aires, Facultad de Medicina, Departamento de Fisiología, Bs As, Argentina
Universidad de Buenos Aires, Facultad de Medicina, Departamento de Biología Celular, Histología, Embriología y Genética, Bs As, Argentina
Palabras clave:Adolescence; Alcohol preference; Anxiety; Cannabinoid receptor 1 (CB1R); Cannabinoid receptor 2 (CB2R); WIN 55,212-2 (WIN); 2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo[1,2,3 de][1,4]benzoxazine; alcohol; cannabinoid 1 receptor; cannabinoid 2 receptor; endocannabinoid; tryptophan hydroxylase; 2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo[1,2,3 de][1,4]benzoxazine; alcohol; benzoxazine derivative; cannabinoid receptor; cannabinoid receptor agonist; central depressant agent; morpholine derivative; naphthalene derivative; serotonin; adolescent; alcohol abuse; alcohol consumption; animal cell; animal experiment; animal model; animal tissue; anxiety; Article; CD-1 mouse; cell interaction; central nervous system; controlled study; dendritic spine; drug abuse; drug dependence; drug exposure; drug sensitivity; food preference; immunohistochemistry; male; modulation; morphometry; mouse; nerve cell; nerve cell differentiation; nerve stimulation; nonhuman; nucleus accumbens; postsynaptic membrane; priority journal; protein expression; raphe nucleus; reward; serotoninergic nerve cell; substantia nigra pars compacta; treatment withdrawal; ventral tegmentum; animal; anxiety; dorsal raphe nucleus; drinking behavior; drug effect; etiology; growth, development and aging; metabolism; pathology; randomization; sexual maturation; Alcohol Drinking; Animals; Anxiety; Benzoxazines; Cannabinoid Receptor Agonists; Central Nervous System Depressants; Dorsal Raphe Nucleus; Ethanol; Male; Mice; Morpholines; Naphthalenes; Neurons; Pars Compacta; Random Allocation; Receptors, Cannabinoid; Serotonin; Sexual Maturation; Ventral Tegmental Area
Año:2018
Volumen:137
Página de inicio:268
Página de fin:274
DOI: http://dx.doi.org/10.1016/j.neuropharm.2018.05.018
Título revista:Neuropharmacology
Título revista abreviado:Neuropharmacology
ISSN:00283908
CODEN:NEPHB
CAS:2,3 dihydro 5 methyl 3 (morpholinomethyl) 6 (1 naphthoyl)pyrrolo[1,2,3 de][1,4]benzoxazine, 134959-51-6; alcohol, 64-17-5; tryptophan hydroxylase, 9037-21-2; serotonin, 50-67-9; Benzoxazines; Cannabinoid Receptor Agonists; Central Nervous System Depressants; Ethanol; Morpholines; Naphthalenes; Receptors, Cannabinoid; Serotonin; Win 55212-2
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v137_n_p268_Frontera

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Citas:

---------- APA ----------
Frontera, J.L., Gonzalez Pini, V.M., Messore, F.L. & Brusco, A. (2018) . Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice. Neuropharmacology, 137, 268-274.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.018
---------- CHICAGO ----------
Frontera, J.L., Gonzalez Pini, V.M., Messore, F.L., Brusco, A. "Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice" . Neuropharmacology 137 (2018) : 268-274.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.018
---------- MLA ----------
Frontera, J.L., Gonzalez Pini, V.M., Messore, F.L., Brusco, A. "Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice" . Neuropharmacology, vol. 137, 2018, pp. 268-274.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.018
---------- VANCOUVER ----------
Frontera, J.L., Gonzalez Pini, V.M., Messore, F.L., Brusco, A. Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice. Neuropharmacology. 2018;137:268-274.
http://dx.doi.org/10.1016/j.neuropharm.2018.05.018