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The Journal of Neuroscience, October 15, 1998, 18(20):8133-8144
Postsynaptic Mechanisms Underlying Responsiveness of Amygdaloid
Neurons to Nociceptin/Orphanin FQ
Susanne
Meis and
Hans-Christian
Pape
Institut für Physiologie,
Otto-von-Guericke-Universität, D-39120 Magdeburg, Germany
Effects of nociceptin/orphanin FQ (N/OFQ), the endogenous
ligand of the opioid-like orphan receptor (ORL), were investigated in
the rat lateral (AL) and central (ACe) amygdala in
vitro. Approximately 98% of presumed projection neurons in the
AL responded to N/OFQ with an increase in inwardly rectifying potassium
conductance, resulting in an impairment in cell excitability.
Half-maximal effects were obtained at 30.6 nM; the Hill
coefficient was 0.63. In the ACe, 31% of the cells displayed responses
similar to that in the AL, 44% were nonresponsive, and 25% responded
with a small potassium current with a linear current-voltage
relationship. Responses to N/OFQ were reduced by 100 µM
Ba2+, were insensitive to 10 µM
naloxone, and were blocked by a selective ORL antagonist,
[Phe1 (CH2-NH)Gly2]NC(1-13)NH2
(IC50 = 760 nM). Involvement of G-proteins was
indicated by irreversible effects and blockade of action of N/OFQ
during intracellular presence of GTP- -S (100 µM) and
GDP- -S (2 mM), respectively, and prevention of responses
after incubation in pertussis toxin (500 ng/ml). These mechanisms may
contribute to the role of N/OFQ in the reduction of fear responsiveness
and stress that have recently been suggested on the basis of
histochemical and behavioral studies.
Key words:
nociceptin; orphanin FQ; amygdala; electrophysiology; pharmacology; potassium inward rectifier
Copyright © 1998 Society for Neuroscience 0270-6474/98/18208133-12$05.00/0
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