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Interactions between ethanol and the endocannabinoid system at GABAergic synapses on basolateral amygdala principal neurons.
Alcohol. 2015 Dec; 49(8):781-94.A

Abstract

The basolateral amygdala (BLA) plays crucial roles in stimulus value coding, as well as drug and alcohol dependence. Ethanol alters synaptic transmission in the BLA, while endocannabinoids (eCBs) produce presynaptic depression at BLA synapses. Recent studies suggest interactions between ethanol and eCBs that have important consequences for alcohol drinking behavior. To determine how ethanol and eCBs interact in the BLA, we examined the physiology and pharmacology of GABAergic synapses onto BLA pyramidal neurons in neurons from young rats. Application of ethanol at concentrations relevant to intoxication increased, in both young and adult animals, the frequency of spontaneous and miniature GABAergic inhibitory postsynaptic currents, indicating a presynaptic site of ethanol action. Ethanol did not potentiate sIPSCs during inhibition of adenylyl cyclase while still exerting its effect during inhibition of protein kinase A. Activation of type 1 cannabinoid receptors (CB1) in the BLA inhibited GABAergic transmission via an apparent presynaptic mechanism, and prevented ethanol potentiation. Surprisingly, ethanol potentiation was also prevented by CB1 antagonists/inverse agonists. Brief depolarization of BLA pyramidal neurons suppressed GABAergic transmission (depolarization-induced suppression of inhibition [DSI]), an effect previously shown to be mediated by postsynaptic eCB release and presynaptic CB1 activation. A CB1-mediated suppression of GABAergic transmission was also produced by combined afferent stimulation at 0.1 Hz (LFS), and postsynaptic loading with the eCB arachidonoyl ethanolamide (AEA). Both DSI and LFS-induced synaptic depression were prevented by ethanol. Our findings indicate antagonistic interactions between ethanol and eCB/CB1 modulation at GABAergic BLA synapses that may contribute to eCB roles in ethanol seeking and drinking.

Authors+Show Affiliations

Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA; Institute of Neuroscience, National Research Council, Monserrato, Cagliari, Italy.Section on Synaptic Pharmacology, Laboratory for Integrative Neuroscience, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: lovindav@mail.nih.gov.

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural

Language

eng

PubMed ID

26603632

Citation

Talani, Giuseppe, and David M. Lovinger. "Interactions Between Ethanol and the Endocannabinoid System at GABAergic Synapses On Basolateral Amygdala Principal Neurons." Alcohol (Fayetteville, N.Y.), vol. 49, no. 8, 2015, pp. 781-94.
Talani G, Lovinger DM. Interactions between ethanol and the endocannabinoid system at GABAergic synapses on basolateral amygdala principal neurons. Alcohol. 2015;49(8):781-94.
Talani, G., & Lovinger, D. M. (2015). Interactions between ethanol and the endocannabinoid system at GABAergic synapses on basolateral amygdala principal neurons. Alcohol (Fayetteville, N.Y.), 49(8), 781-94. https://doi.org/10.1016/j.alcohol.2015.08.006
Talani G, Lovinger DM. Interactions Between Ethanol and the Endocannabinoid System at GABAergic Synapses On Basolateral Amygdala Principal Neurons. Alcohol. 2015;49(8):781-94. PubMed PMID: 26603632.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between ethanol and the endocannabinoid system at GABAergic synapses on basolateral amygdala principal neurons. AU - Talani,Giuseppe, AU - Lovinger,David M, Y1 - 2015/10/27/ PY - 2015/04/14/received PY - 2015/08/11/revised PY - 2015/08/25/accepted PY - 2015/11/26/entrez PY - 2015/11/26/pubmed PY - 2016/9/28/medline KW - Alcohol KW - Arachidonoyl ethanolamide KW - CB1 receptor KW - Cyclic AMP KW - Inhibition KW - Synapse SP - 781 EP - 94 JF - Alcohol (Fayetteville, N.Y.) JO - Alcohol VL - 49 IS - 8 N2 - The basolateral amygdala (BLA) plays crucial roles in stimulus value coding, as well as drug and alcohol dependence. Ethanol alters synaptic transmission in the BLA, while endocannabinoids (eCBs) produce presynaptic depression at BLA synapses. Recent studies suggest interactions between ethanol and eCBs that have important consequences for alcohol drinking behavior. To determine how ethanol and eCBs interact in the BLA, we examined the physiology and pharmacology of GABAergic synapses onto BLA pyramidal neurons in neurons from young rats. Application of ethanol at concentrations relevant to intoxication increased, in both young and adult animals, the frequency of spontaneous and miniature GABAergic inhibitory postsynaptic currents, indicating a presynaptic site of ethanol action. Ethanol did not potentiate sIPSCs during inhibition of adenylyl cyclase while still exerting its effect during inhibition of protein kinase A. Activation of type 1 cannabinoid receptors (CB1) in the BLA inhibited GABAergic transmission via an apparent presynaptic mechanism, and prevented ethanol potentiation. Surprisingly, ethanol potentiation was also prevented by CB1 antagonists/inverse agonists. Brief depolarization of BLA pyramidal neurons suppressed GABAergic transmission (depolarization-induced suppression of inhibition [DSI]), an effect previously shown to be mediated by postsynaptic eCB release and presynaptic CB1 activation. A CB1-mediated suppression of GABAergic transmission was also produced by combined afferent stimulation at 0.1 Hz (LFS), and postsynaptic loading with the eCB arachidonoyl ethanolamide (AEA). Both DSI and LFS-induced synaptic depression were prevented by ethanol. Our findings indicate antagonistic interactions between ethanol and eCB/CB1 modulation at GABAergic BLA synapses that may contribute to eCB roles in ethanol seeking and drinking. SN - 1873-6823 UR - https://www.unboundmedicine.com/medline/citation/26603632/Interactions_between_ethanol_and_the_endocannabinoid_system_at_GABAergic_synapses_on_basolateral_amygdala_principal_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0741-8329(15)30019-7 DB - PRIME DP - Unbound Medicine ER -