PT - JOURNAL ARTICLE AU - CD Fiorillo AU - JT Williams TI - Opioid desensitization: interactions with G-protein-coupled receptors in the locus coeruleus AID - 10.1523/JNEUROSCI.16-04-01479.1996 DP - 1996 Feb 15 TA - The Journal of Neuroscience PG - 1479--1485 VI - 16 IP - 4 4099 - http://www.jneurosci.org/content/16/4/1479.short 4100 - http://www.jneurosci.org/content/16/4/1479.full SO - J. Neurosci.1996 Feb 15; 16 AB - 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.