title: Nociceptin/orphanin FQ blockade of corticotropin-releasing factor-induced gamma-aminobutyric acid release in central amygdala is enhanced after chronic ethanol exposure.
abstract: BACKGROUND
  The central nucleus of the amygdala (CeA) mediates stress- and addiction-related processes. Corticotropin-releasing factor (CRF) and nociceptin/orphanin FQ (nociceptin) regulate ethanol intake and anxiety-like behavior. In the rat, CRF and ethanol significantly augment CeA gamma-aminobutyric acid (GABA) release, whereas nociceptin diminishes it.
  
  
  METHODS
  Using electrophysiologic techniques in an in vitro slice preparation, we investigated the interaction of nociceptin and CRF on evoked and spontaneous GABAergic transmission in CeA slices of naive and ethanol-dependent rats and the mechanistic role of protein kinase A.
  
  
  RESULTS
  In neurons from naive animals, nociceptin dose-dependently diminished basal-evoked GABA(A) receptor-mediated inhibitory postsynaptic potentials (IPSPs) by decreasing GABA release and prevented, as well as reversed, CRF-induced augmentation of IPSPs, actions that required PKA signaling. In neurons from ethanol-dependent animals, nociceptin decreased basal GABAergic transmission and blocked the CRF-induced increase in GABA release to a greater extent than in naive controls.
  
  
  CONCLUSIONS
  These data provide new evidence for an interaction between the nociceptin and CRF systems in the CeA. Nociceptin opposes CRF effects on CeA GABAergic transmission with sensitization of this effect in dependent animals. These properties of nociceptin may underlie its anti-alcohol and anxiolytic properties and identify the nociceptin receptor as a useful therapeutic target for alcoholism.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Maureen T
authors.initials: MT
authors.lastname: Cruz
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Herman
authors.forename: Marsida
authors.initials: M
authors.lastname: Kallupi
authors.forename: Marisa
authors.initials: M
authors.lastname: Roberto
mesh_terms: D000437:Alcoholism / Q000378:metabolism; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D000431:Ethanol / Q000494:pharmacology*; D018682:GABA Agents / Q000378:metabolism; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D018847:Opioid Peptides / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000097629:Nociceptin
chemical_list: D002492:Central Nervous System Depressants; D003346:Corticotropin-Releasing Hormone; D017868:Cyclic AMP-Dependent Protein Kinases; D000431:Ethanol; D018682:GABA Agents; D018847:Opioid Peptides; D005680:gamma-Aminobutyric Acid; D000097629:Nociceptin