Time course study of changes in the activity of the catecholamine synthesizing enzymes in the rat medulla oblongata after intraventricular injection of 6-hydroxydopamine

Abstract

Recent data have shown that 5 days after intraventricular injection of 6-hydroxydopamine (6-OHDA), the tyrosine hydroxylase activity (TH) was increased within the locus coeruleus (LC). We sought to determine if such an alteration occurs within the A1 and A2 noradrenergic (NA) and C1 and C2 adrenergic (A) neurons of the rat medulla oblongata. The TH activity within the cell bodies was significantly increased 2 days after 6-OHDA injection with a maximum at 5 days (LC, + 109%, P < 0.001;A1-C1, +40%, P < 0.01;A 2-C 2; + 24%, P < 0.01) while a significant decrease was present 21 days after 6-OHDA. Conversely, dopamine-β-hydroxylase (DBH) activity exhibited a decrease which was maximal at 21 days (LC, −41%;A1-C1, −33%,A2-C2, −35%, P < 0.001). Both the TH (−47% at 5 days) and the DBH (−82% at 12 days) activities were decreased within the terminals of the tractus intermediolateralis (TIML). The phenylethanolamine-N-methyltransferase (PNMT) activity was never altered in the cell bodies nor in the terminals analyzed. These data demonstrate that the NA neurons of the rat medulla oblongata and of the LC exhibit a similar pattern of response to the neurotoxin 6-OHDA. Conversely, the lack of change in the PNMT activity confirms the hypothesis of a resistance of the A neurons to 6-OHDA or questions the validity of the PNMT as an A marker.