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Biol Psychiatry. 2012 Apr 15;71(8):666-76. doi: 10.1016/j.biopsych.2011.10.032. Epub 2011 Dec 6.

Nociceptin/orphanin FQ blockade of corticotropin-releasing factor-induced gamma-aminobutyric acid release in central amygdala is enhanced after chronic ethanol exposure.

Author information

1
Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.

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.

PMID:
22153590
PMCID:
PMC3838304
DOI:
10.1016/j.biopsych.2011.10.032
[Indexed for MEDLINE]
Free PMC Article

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