The Journal of Neuroscience, March 1, 1998, 18(5):1671-1678
µ-Opioid Peptides Inhibit Thalamic Neurons
Jennifer
Brunton1, 2 and
Serge
Charpak1, 2
1 Department of Physiology, University Medical Center,
1211 Geneva 4, Switzerland, and 2 Laboratoire de
Physiologie, Ecole Supérieure de Physique et de Chimie
Industrielles, Centre National de la Recherche Scientifique,
Unité de Recherche Associée 2054, 75005 Paris, France
Opioidergic inhibition of neurons in the centrolateral nucleus of
the thalamus was investigated using an in vitro thalamic slice preparation from young rats. The µ-opioid receptor agonist D-Ala2,N-Me-Phe4,glycinol5-enkephalin
(DAMGO) evoked a hyperpolarization and decrease in input resistance
that was reversible, concentration-dependent, and persisted in the
presence of tetrodotoxin. Application of the specific µ-receptor
antagonist
Cys2,Tyr3,Orn5,Pen7-amide
blocked this response. The respective 
- and 
-opioid receptor agonists,
(D-Pen2,D-Pen5)-enkephalin
and (±)-trans-U-50488 methanesulfonate had no effect. Voltage-clamp experiments showed that DAMGO activated an inwardly rectifying potassium conductance
(GKIR) characterized by rectification at hyperpolarized potentials that increased in elevated extracellular potassium concentrations, a complete block by Ba2+
(1 mM), and a voltage-dependent block by
Cs+. The extent of µ-opioid inhibition in other
thalamic nuclei was then investigated. Widespread inhibition similar to
that seen in the centrolateral nucleus was observed in a number of
sensory, motor, intralaminar, and midline nuclei. Our results suggest
that the net action of opioids would depend on their source: exogenous (systemically administered) opiates inhibiting the entire thalamus and
favoring the shift of cell firing from tonic to bursting mode; and
endogenously released opioids acting on specific thalamic nuclei, their
release depending on the origin of the presynaptic input.
Key words:
µ-opioids; inhibition; thalamus; intralaminar nuclei; centrolateral nucleus; inwardly rectifying potassium conductance; cesium
Copyright © 1998 Society for Neuroscience 0270-6474/98/1851671-08$05.00/0
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