Morphine actions in the rat forebrain: role of protein kinase C.
Acute administration of morphine induces expression of the immediate-early gene (IEG) c-Fos in dorsomedial striatum, portions of cerebral cortex, and in several midline-intralaminar thalamic nuclei, partly via a trans-synaptic mechanism that involves activation of glutamate receptors. Because activation of protein kinase C (PKC) may occur following the activation of glutamate receptors, we determined whether pharmacological inhibition of PKC would attenuate morphine-induced c-Fos expression, and whether acute administration of morphine would induce translocation of PKC. The selective PKC antagonist NPC 15437 given 30 min prior to morphine significantly decreased morphine-induced c-Fos expression in striatum and cingulate cortex, but not in centrolateral thalamus. In another experiment, rats were given an acute dose of morphine, and immunocytochemical analysis was performed for the betaI and betaII isoforms of PKC. Morphine induced a rapid and transient translocation of PKC betaII, but not betaI, from perinuclear spots to plasma membrane in numerous cortical and striatal neurons. Prior administration of naloxone blocked this response. Ultrastructural studies confirmed translocation from Golgi apparatus to plasma membrane 15 min after morphine injection. Double immunocytochemistry at the light microscopic level demonstrated co-localization of translocated PKC betaII and c-Fos in some cortical neurons 90 min after morphine injection. These results support a role for PKC, especially PKC betaII, in the rapid effects of morphine on the brain.
Harlan
Richard E
RE
Department of Structural and Cellular Biology, Tulane University School of Medicine, 1430 Tulane Avenue, SL-49, New Orleans, LA 70112, USA. harlanere@tulane.edu
Kailas
Sudha R
SR
Tagoe
C E F
CE
Garcia
Meredith M
MM
D000818:Animals; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D016548:Prosencephalon / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology*; D011493:Protein Kinase C / Q000032:analysis / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D009020:Morphine; D011493:Protein Kinase C