CHANGES IN THE RETENTION AND METABOLISM OF ³H-l-NOREPINEPHRINE IN RAT BRAIN IN VIVO AFTER 6-HYDROXYDOPAMINE PRETREATMENT

¹ Department of Pharmacology, University of Cambridge, Cambridge, England

Rats were injected intraventricularly with ³H-l-norepinephrine (NE) three weeks after intraventricular injections of 6-hydroxydopamine (6-OHDA), which cause a selective degeneration of catecholamine nerve terminals in the central nervous system. There was a marked decrease in the retention of ⁸H-NE in the brains of treated animals. This was associated with an increase in ⁸H-deaminated metabolites and ⁸H-normetanephrine. Reserpine treatment reduced the retention of ⁸H-NE even further in 6-OHDA-treated rats, the percent reduction being similar to that in reserpinetreated control rats. The retention of ⁸H-NE was significantly reduced in hypothalamus and striatum but not in the pons-medulla region of 6-OHDA-treated brains. The initial rates of uptake of ⁸H-NE into slices prepared from these three brain regions were reduced by 6-OHDA, suggesting a loss of NE uptake sites. The subcellular distribution (particulate/supernatant ratio) of ³H-NE retained in the hypothalamus, striatum and pons-medulla of treated animals was similar to that of controls. The rate constant of disappearance of ⁸H-NE was increased by 6-OHDA treatment in striatum and pons-medulla, although the rate of NE turnover was much lower in all brain regions of treated animals than in controls. These results support the view that intraventricularly injected ⁸H-NE is selectively accumulated by catecholamine-containing neurons. The ⁸H-NE that is retained by the brains of 6-OHDA-treated animals is probably located in the catecholamine neurons that survived the degenerative effects of 6-OHDA treatment.

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