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The endocannabinoid system tonically regulates inhibitory transmission and depresses the effect of ethanol in central amygdala.
Neuropsychopharmacology. 2010 Aug; 35(9):1962-72.N

Abstract

The central amygdala (CeA) has a major role in alcohol dependence and reinforcement, and behavioral and neurochemical evidence suggests a role for the endocannabinoid (eCB) system in ethanol binging and dependence. We used a slice preparation to investigate the physiological role of cannabinoids and their interaction with ethanol on inhibitory synaptic transmission in CeA. Superfusion of the cannabinoid receptor (CB1) agonist WIN55212-2 (WIN2) onto CeA neurons decreased evoked GABA(A) receptor-mediated inhibitory postsynaptic potentials (IPSPs) in a concentration-dependent manner, an effect prevented by the CB1 antagonists Rimonabant (SR141716, SR1) and AM251. SR1 or AM251 applied alone augmented IPSPs, revealing a tonic eCB activity that decreased inhibitory transmission in CeA. Paired-pulse analysis suggested a presynaptic CB1 mechanism. Intracellular BAPTA abolished the ability of AM251 to augment IPSPs, demonstrating the eCB-driven nature and postsynaptic origin of the tonic CB1-dependent control of GABA release. Superfusion of ethanol increased IPSPs and addition of WIN2 reversed the ethanol effect. Similarly, previous superfusion of WIN2 prevented subsequent ethanol effects on GABAergic transmission. The ethanol-induced augmentation of IPSPs was additive to CB1 blockade, ruling out a participation of CB1 in the action of acute ethanol. Our study points to an important role of CB1 in CeA in which the eCBs tonically regulate neuronal activity, and suggests a potent mechanism for modulating CeA tone during challenge with ethanol.

Authors+Show Affiliations

Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, California 92037, USA.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

Language

eng

PubMed ID

20463657

Citation

Roberto, Marisa, et al. "The Endocannabinoid System Tonically Regulates Inhibitory Transmission and Depresses the Effect of Ethanol in Central Amygdala." Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, vol. 35, no. 9, 2010, pp. 1962-72.
Roberto M, Cruz M, Bajo M, et al. The endocannabinoid system tonically regulates inhibitory transmission and depresses the effect of ethanol in central amygdala. Neuropsychopharmacology. 2010;35(9):1962-72.
Roberto, M., Cruz, M., Bajo, M., Siggins, G. R., Parsons, L. H., & Schweitzer, P. (2010). The endocannabinoid system tonically regulates inhibitory transmission and depresses the effect of ethanol in central amygdala. Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology, 35(9), 1962-72. https://doi.org/10.1038/npp.2010.70
Roberto M, et al. The Endocannabinoid System Tonically Regulates Inhibitory Transmission and Depresses the Effect of Ethanol in Central Amygdala. Neuropsychopharmacology. 2010;35(9):1962-72. PubMed PMID: 20463657.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoid system tonically regulates inhibitory transmission and depresses the effect of ethanol in central amygdala. AU - Roberto,Marisa, AU - Cruz,Maureen, AU - Bajo,Michal, AU - Siggins,George R, AU - Parsons,Loren H, AU - Schweitzer,Paul, Y1 - 2010/05/12/ PY - 2010/5/14/entrez PY - 2010/5/14/pubmed PY - 2010/10/29/medline SP - 1962 EP - 72 JF - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JO - Neuropsychopharmacology VL - 35 IS - 9 N2 - The central amygdala (CeA) has a major role in alcohol dependence and reinforcement, and behavioral and neurochemical evidence suggests a role for the endocannabinoid (eCB) system in ethanol binging and dependence. We used a slice preparation to investigate the physiological role of cannabinoids and their interaction with ethanol on inhibitory synaptic transmission in CeA. Superfusion of the cannabinoid receptor (CB1) agonist WIN55212-2 (WIN2) onto CeA neurons decreased evoked GABA(A) receptor-mediated inhibitory postsynaptic potentials (IPSPs) in a concentration-dependent manner, an effect prevented by the CB1 antagonists Rimonabant (SR141716, SR1) and AM251. SR1 or AM251 applied alone augmented IPSPs, revealing a tonic eCB activity that decreased inhibitory transmission in CeA. Paired-pulse analysis suggested a presynaptic CB1 mechanism. Intracellular BAPTA abolished the ability of AM251 to augment IPSPs, demonstrating the eCB-driven nature and postsynaptic origin of the tonic CB1-dependent control of GABA release. Superfusion of ethanol increased IPSPs and addition of WIN2 reversed the ethanol effect. Similarly, previous superfusion of WIN2 prevented subsequent ethanol effects on GABAergic transmission. The ethanol-induced augmentation of IPSPs was additive to CB1 blockade, ruling out a participation of CB1 in the action of acute ethanol. Our study points to an important role of CB1 in CeA in which the eCBs tonically regulate neuronal activity, and suggests a potent mechanism for modulating CeA tone during challenge with ethanol. SN - 1740-634X UR - https://www.unboundmedicine.com/medline/citation/20463657/The_endocannabinoid_system_tonically_regulates_inhibitory_transmission_and_depresses_the_effect_of_ethanol_in_central_amygdala_ L2 - http://dx.doi.org/10.1038/npp.2010.70 DB - PRIME DP - Unbound Medicine ER -