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Journal of Neuroscience, Vol 16, 1479-1485, Copyright © 1996 by Society for Neuroscience
Opioid desensitization: interactions with G-protein-coupled receptors in the locus coeruleus
CD Fiorillo and JT Williams
Vollum Institute, Oregon Health Sciences University, Portland 97201, USA.
In rat locus coeruleus (LC) neurons, alpha 2 adrenoceptors, mu-opioid and
somatostatin receptors all activate the same potassium conductance. Chronic
treatment with morphine causes a loss of sensitivity that is specific to
the mu-opioid response, with no change in the alpha 2 adrenoceptor-mediated
response. Acute desensitization induced by opioid, somatostatin, and alpha
2-adrenoceptor agonists was studied in brain slices of rat LC using
intracellular recording. A supramaximal concentration of the opioid agonist
Met5-enkephalin induced a profound homologous desensitization but little
heterologous desensitization to an alpha 2-adrenoceptor agonist (UK 14304)
or somatostatin. All desensitized currents showed partial recovery. A
supramaximal concentration of UK14304 caused a relatively small amount of
desensitization. Although little interaction was observed among inhibitory
G-protein-coupled receptors, activation of an excitatory receptor had
marked effects on inhibitory responses. Muscarinic agonists, which produce
an inward current in LC neurons, reduced the magnitude of agonist-induced
outward currents and increased both the rate and amount of opioid
desensitization. Muscarinic activation did not alter desensitization of
alpha 2-adrenoceptor responses. Acute desensitization shares several
characteristics with the tolerance induced by chronic morphine treatment of
animals.
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