title: Interactions between ethanol and the endocannabinoid system at GABAergic synapses on basolateral amygdala principal neurons.
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.affiliation: 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.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Talani
authors.affiliation: 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.
authors.forename: David M
authors.initials: DM
authors.lastname: Lovinger
mesh_terms: D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D066272:Basolateral Nuclear Complex / Q000187:drug effects* / Q000378:metabolism; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D016048:Dideoxyadenosine / Q000494:pharmacology; D063388:Endocannabinoids / Q000378:metabolism / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D059330:GABAergic Neurons / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors; D043882:Receptors, Cannabinoid / Q000187:drug effects* / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D000963:Antimetabolites; D001095:Arachidonic Acids; D063386:Cannabinoid Receptor Agonists; D002492:Central Nervous System Depressants; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D047428:Protein Kinase Inhibitors; D043884:Receptor, Cannabinoid, CB1; D043882:Receptors, Cannabinoid; D000431:Ethanol; D016048:Dideoxyadenosine; C078814:anandamide
keywords: Alcohol; Arachidonoyl ethanolamide; CB1 receptor; Cyclic AMP; Inhibition; Synapse