Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice
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 predominantl...
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2018
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v137_n_p268_Frontera http://hdl.handle.net/20.500.12110/paper_00283908_v137_n_p268_Frontera |
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paper:paper_00283908_v137_n_p268_Frontera2023-06-08T14:55:08Z Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice 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 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 2018 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v137_n_p268_Frontera http://hdl.handle.net/20.500.12110/paper_00283908_v137_n_p268_Frontera |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice |
| topic_facet |
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 |
| description |
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 |
| title |
Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice |
| title_short |
Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice |
| title_full |
Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice |
| title_fullStr |
Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice |
| title_full_unstemmed |
Exposure to cannabinoid agonist WIN 55,212-2 during early adolescence increases alcohol preference and anxiety in CD1 mice |
| title_sort |
exposure to cannabinoid agonist win 55,212-2 during early adolescence increases alcohol preference and anxiety in cd1 mice |
| publishDate |
2018 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00283908_v137_n_p268_Frontera http://hdl.handle.net/20.500.12110/paper_00283908_v137_n_p268_Frontera |
| _version_ |
1768544810757521408 |