Effects of intraventricular 2,4,5-trihydroxyphenylethylamine (6-hydroxydopamine) on rat behaviour and brain catecholamine metabolism.

1. 6-Hydroxydopamine (200 mug injected intraventricularly) caused depletion of noradrenaline from all regions of rat brain within 2 h after injection but depletion of dopamine in the brain was observed only from 2 days after injection. Both catecholamines remained depleted for more than 32 days.2. Rats treated with intraventricular 6-hydroxydopamine were sedated and lethargic, with reduced spontaneous and exploratory activity, for periods of up to 8 days after injection. Conditioned avoidance responding was abolished or reduced for a similar period.3. Intraventricular 6-hydroxydopamine caused a prolonged reduction in the amount of labelled catecholamines in store 4 h following an intraventricular injection of (3)H-dopamine. During the first 6 h after 6-hydroxydopamine injection, there was a marked increase in neutral and acid metabolites from the labelled catecholamines.4. A comparison of the behavioural and biochemical effects of intraventricular 6-hydroxydopamine and reserpine suggests that both drugs affect catecholamine storage mechanisms but by different mechanisms. It was not possible from these experiments to correlate behavioural changes with either catecholamine storage or metabolism.