Attenuation of morphine withdrawal by injection of a protein kinase inhibitor into the locus coeruleus and the periaqueductal gray matter

Abstract

Protein kinases have been suggested to participate in the adaptative changes leading to opiate dependence. Thus, chronic morphine induced a selective increase on cAMP-dependent protein kinase (PKA) activity in the locus coeruleus (LC) (1). The aim of this study was to evaluate the role played on the behavioral expression of morphine withdrawal by the protein kinases in the LC and the periaqueductal gray matter (PAG). Physical dependence was induced in rats by chronic peripheral administration of morphine. The effects induced by the microinjection of the protein kinase inhibitor H7 into the LC and the PAG on naloxone-precipitated withdrawal syndrome was investigated. H7 administration into the LC induced a strong attenuation of morphine withdrawal. Signs related to the motor component of abstinence were the most severely reduced. A similar result was observed after the injection of H7 into the PAG, but in this case motor signs were less strongly reduced and the attenuation was more widespread. These results indicate that protein kinases in the LC and the PAG are directly implicated in the behavioral expression of morphine withdrawal syndrome.