EFFECTS OF 6‐HYDROXYDOPAMINE ON CATECHOLAMINE CONTAINING NEURONES IN THE RAT BRAIN

Abstract

After the intraventricular injection of 6‐hydroxydopamine (6‐OHDA), there was a long lasting reduction in the brain concentrations of noradrenaline (NA) and dopamine (DA). The brain concentration of NA was affected by lower doses of 6‐OHDA than were required to deplete DA. A high dose of 6‐OHDA which depleted the brain of NA and DA by 81 per cent and 66 per cent respectively, had no significant effect on brain concentrations of 5‐hydroxytryptamine (5‐HT) or γ‐aminobutyric acid (GABA). The fall in catecholamines was accompanied by a long lasting reduction in the activities of tyrosine hydroxylase and DOPA decarboxylase in the hypothalamus and striatum, areas in the brain which are rich in catecholamine containing nerve endings. There was, however, no consistent effect on catechol‐O‐methyl transferase or monamine oxidase activity in these brain regions. The initial accumulation of [3 H]NA into slices of the hypothalamus and striatum was markedly reduced 22–30 days after 6‐OHDA treatment. These results are consistent with the evidence in the peripheral sympathetic nervous system that 6‐OHDA causes a selective destruction of adrenergic nerve endings and suggest that this compound may have a similar destructive effect on catecholamine neurones in the CNS.