CHRONIC MORPHINE ADMINISTRATION INCREASES BETA-ADRENERGIC-RECEPTOR KINASE (BETA-ARK) LEVELS IN THE RAT LOCUS-COERULEUS

Based on the established role of beta-adrenergic receptor kinase (beta ARK) and beta-arrestin in the desensitization of several G protein-co upled receptors, we investigated the effect of chronic morphine admini stration on beta ARK and beta-arrestin levels in selected brain areas. Levels of beta ARK were measured by blot immunolabeling analysis usin g antibodies specific for two known forms of beta ARK, i.e., beta ARK1 and beta ARK2. It was found that chronic morphine treatment produced an similar to 35% increase in levels of beta ARK1 immunoreactivity in the locus coeruleus, but not in several other brain regions studied. I n contrast, chronic morphine treatment failed to alter levels of beta ARK2 immunoreactivity in any of the brain regions studied. Levels of b eta-arrestin immunoreactivity, measured using an antiserum that recogn izes two major forms of this protein in brain, were also found to incr ease (by similar to 20%) in the locus coeruleus. It is proposed that c hronic morphine regulation of beta ARK1 and beta-arrestin levels may c ontribute to opioid-receptor tolerance that is known to occur in this brain region.