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CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats.
Neuropharmacology 2008; 54(6):976-88N

Abstract

There is strong evidence that blocking CB1 receptors may reduce alcohol intake in alcohol-dependent individuals. However, there is still limited evidence that CB1 receptor antagonists may also be beneficial in the attenuation of alcohol withdrawal syndrome, even though alcohol withdrawal appears to be milder in CB1 receptor knockout mice. Here we have examined whether the CB1 receptor antagonist rimonabant (SR141716) can alleviate the behavioral symptoms and revert the neurochemical imbalance elicited by a 3-h interruption of chronic alcohol exposure (7.2% in the drinking water for 10 days) in male Wistar rats. Administration of rimonabant attenuated the strong anxiogenic traits of the animals that developed when regular alcohol intake was interrupted. This may reflect the correction of the GABA/glutamate imbalances developed by the animals that received rimonabant in various brain regions involved in emotional (e.g. prefrontal cortex) and motor (e.g. caudate-putamen and globus pallidus) responses. In addition, rimonabant also affected the dopamine deficits generated by alcohol abstinence in the amygdala and ventral-tegmental area, albeit to a lesser extent. However, this antagonist was unable to correct the impairment caused by alcohol abstinence in serotonin and neuropeptide Y. The endocannabinoid activity in the brain of alcohol-abstinent rats indicated that the behavioral and neurochemical improvements caused by rimonabant were not related to the attenuation of a possible increase in this activity generated by alcohol withdrawal. Conversely, the density of CB1 receptors was reduced in alcohol-abstinent animals (e.g. globus pallidus, substantia nigra), as were the levels of endocannabinoids and related N-acylethanolamines (e.g. amygdala, caudate-putamen). Thus, rimonabant possibly enhances an endogenous response generated by interrupting the regular use of alcohol. In summary, rimonabant might attenuate withdrawal symptoms associated with alcohol abstinence, an effect that was presumably due to the normalization of GABA and glutamate, and to a lesser extent, dopamine transmission in emotion- and motor-related areas.

Authors+Show Affiliations

Departamento de Bioquímica y Biología Molecular and Centro de Investigación biomédica en Red sobre Enfermedades Neurodegenerativas, Facultad de Medicina, Universidad Complutense, 28040-Madrid, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18371990

Citation

Rubio, Marina, et al. "CB1 Receptor Blockade Reduces the Anxiogenic-like Response and Ameliorates the Neurochemical Imbalances Associated With Alcohol Withdrawal in Rats." Neuropharmacology, vol. 54, no. 6, 2008, pp. 976-88.
Rubio M, Fernández-Ruiz J, de Miguel R, et al. CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology. 2008;54(6):976-88.
Rubio, M., Fernández-Ruiz, J., de Miguel, R., Maestro, B., Michael Walker, J., & Ramos, J. A. (2008). CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. Neuropharmacology, 54(6), pp. 976-88. doi:10.1016/j.neuropharm.2008.02.005.
Rubio M, et al. CB1 Receptor Blockade Reduces the Anxiogenic-like Response and Ameliorates the Neurochemical Imbalances Associated With Alcohol Withdrawal in Rats. Neuropharmacology. 2008;54(6):976-88. PubMed PMID: 18371990.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CB1 receptor blockade reduces the anxiogenic-like response and ameliorates the neurochemical imbalances associated with alcohol withdrawal in rats. AU - Rubio,Marina, AU - Fernández-Ruiz,Javier, AU - de Miguel,Rosario, AU - Maestro,Begoña, AU - Michael Walker,J, AU - Ramos,José A, Y1 - 2008/02/16/ PY - 2007/09/19/received PY - 2008/02/05/revised PY - 2008/02/06/accepted PY - 2008/3/29/pubmed PY - 2008/7/23/medline PY - 2008/3/29/entrez SP - 976 EP - 88 JF - Neuropharmacology JO - Neuropharmacology VL - 54 IS - 6 N2 - There is strong evidence that blocking CB1 receptors may reduce alcohol intake in alcohol-dependent individuals. However, there is still limited evidence that CB1 receptor antagonists may also be beneficial in the attenuation of alcohol withdrawal syndrome, even though alcohol withdrawal appears to be milder in CB1 receptor knockout mice. Here we have examined whether the CB1 receptor antagonist rimonabant (SR141716) can alleviate the behavioral symptoms and revert the neurochemical imbalance elicited by a 3-h interruption of chronic alcohol exposure (7.2% in the drinking water for 10 days) in male Wistar rats. Administration of rimonabant attenuated the strong anxiogenic traits of the animals that developed when regular alcohol intake was interrupted. This may reflect the correction of the GABA/glutamate imbalances developed by the animals that received rimonabant in various brain regions involved in emotional (e.g. prefrontal cortex) and motor (e.g. caudate-putamen and globus pallidus) responses. In addition, rimonabant also affected the dopamine deficits generated by alcohol abstinence in the amygdala and ventral-tegmental area, albeit to a lesser extent. However, this antagonist was unable to correct the impairment caused by alcohol abstinence in serotonin and neuropeptide Y. The endocannabinoid activity in the brain of alcohol-abstinent rats indicated that the behavioral and neurochemical improvements caused by rimonabant were not related to the attenuation of a possible increase in this activity generated by alcohol withdrawal. Conversely, the density of CB1 receptors was reduced in alcohol-abstinent animals (e.g. globus pallidus, substantia nigra), as were the levels of endocannabinoids and related N-acylethanolamines (e.g. amygdala, caudate-putamen). Thus, rimonabant possibly enhances an endogenous response generated by interrupting the regular use of alcohol. In summary, rimonabant might attenuate withdrawal symptoms associated with alcohol abstinence, an effect that was presumably due to the normalization of GABA and glutamate, and to a lesser extent, dopamine transmission in emotion- and motor-related areas. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/18371990/CB1_receptor_blockade_reduces_the_anxiogenic_like_response_and_ameliorates_the_neurochemical_imbalances_associated_with_alcohol_withdrawal_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(08)00046-4 DB - PRIME DP - Unbound Medicine ER -