title: Nociceptin/orphanin FQ decreases glutamate transmission and blocks ethanol-induced effects in the central amygdala of naive and ethanol-dependent rats.
abstract: The central nucleus of the amygdala (CeA) mediates several addiction-related processes and nociceptin/orphanin FQ (nociceptin) regulates ethanol intake and anxiety-like behaviors. Glutamatergic synapses, in the CeA and throughout the brain, are very sensitive to ethanol and contribute to alcohol reinforcement, tolerance, and dependence. Previously, we reported that in the rat CeA, acute and chronic ethanol exposures significantly decrease glutamate transmission by both pre- and postsynaptic actions. In this study, using electrophysiological techniques in an in vitro CeA slice preparation, we investigated the effects of nociceptin on glutamatergic transmission and its interaction with acute ethanol in naive and ethanol-dependent rats. We found that nociceptin (100-1000 nM) diminished basal-evoked compound glutamatergic receptor-mediated excitatory postsynaptic potentials (EPSPs) and spontaneous and miniature EPSCs (s/mEPSCs) by mainly decreasing glutamate release in the CeA of naive rats. Notably, nociceptin blocked the inhibition induced by acute ethanol (44 mM) and ethanol blocked the nociceptin-induced inhibition of evoked EPSPs in CeA neurons of naive rats. In neurons from chronic ethanol-treated (ethanol-dependent) rats, the nociceptin-induced inhibition of evoked EPSP amplitude was not significantly different from that in naive rats. Application of [Nphe1]Nociceptin(1-13)NH2, a nociceptin receptor (NOP) antagonist, revealed tonic inhibitory activity of NOP on evoked CeA glutamatergic transmission only in ethanol-dependent rats. The antagonist also blocked nociceptin-induced decreases in glutamatergic responses, but did not affect ethanol-induced decreases in evoked EPSP amplitude. Taken together, these studies implicate a potential role for the nociceptin system in regulating glutamatergic transmission and a complex interaction with ethanol at CeA glutamatergic synapses.
authors.affiliation: 1] Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA [2] School of Pharmacy, Pharmacology Unit, University of Camerino, Camerino, Italy.
authors.forename: Marsida
authors.initials: M
authors.lastname: Kallupi
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Florence P
authors.initials: FP
authors.lastname: Varodayan
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Oleata
authors.affiliation: 1] Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA [2] Department of Pharmacology, Universidade Federal do Paraná, Jardim das Américas, Curitiba, Paraná, Brazil.
authors.forename: Diego
authors.initials: D
authors.lastname: Correia
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: George
authors.initials: G
authors.lastname: Luu
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Roberto
mesh_terms: D019973:Alcohol-Related Disorders / Q000188:drug therapy / Q000503:physiopathology; D000679:Amygdala / Q000187:drug effects* / Q000503:physiopathology; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D004558:Electric Stimulation; D000431:Ethanol / Q000494:pharmacology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018847:Opioid Peptides / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000378:metabolism; D013569:Synapses / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects* / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol; D018698:Glutamic Acid; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat