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
GABAA 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.
Key Words
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Article info
Publication history
Published online: December 08, 2011
Accepted:
October 29,
2011
Received in revised form:
October 26,
2011
Received:
September 9,
2011
Identification
Copyright
© 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
