Degeneration of adrenergic nerves produced by 6-hydroxydopamine

Summary1. 6-Hydroxydopamine (200 jug 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 3H-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.

supporting

confidence: 85%

“…The associated loss of adrenergic function suggested that at the periphery 6HD produces a 'chemical sympathectomy' (Malmfors & Sachs, 1968).…”

mentioning

confidence: 99%

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

Laverty

Taylor

1970

“…6-Hydroxydopamine (6-OH-DA) lowers the NA content of sympathetically innervated tissues (Porter, Totaro & Stone, 1963, Laverty, Sharman & Vogt, 1965Thoenen & Tranzer, 1968) by causing the destruction of the sympathetic nerve endings (Tranzer & Thoenen, 1967;Malmfors & Sachs, 1968). Isolated, perfused hearts from rats pretreated with 6-OH-DA should, therefore, show no intraneuronal uptake (Uptake 1), but only an extraneuronal accumulation (Uptake 2) of catecholamines at all perfusion concentrations.…”

Section: Introductionmentioning

confidence: 99%

Effect of pretreatment with 6‐hydroxydopamine on the uptake and metabolism of catecholamines by the isolated perfused rat heart

Hellmann

Hertting

Peskar

1971

Summary1. Isolated rat hearts from control and 6-hydroxydopamine pretreated animals -were perfused with 3H-noradrenaline or 3H-dopamine, either at a low perfusion concentration (150 x 10-10 mol/ml 3H-dopamine; 1.18 x 10-10 mol/ml 3H-noradrenaline) or a high perfusion concentration (296-69 x 10-10 mol/ml 31H-noradrenaline, 327 45 x 10-10 mol/ml 3H-dopamine) for 8 minutes.2. At the low perfusion concentration, the total activity, the radioactivity in the alumina eluates (sum of 3H-dopamine, 3H-noradrenaline and deaminated catechol metabolites) and the concentration of 3H-dopamine, 3H-noradrenaline and the deaminated catechol metabolites were decreased in the hearts of the pretreated rats as compared with the controls. The 0-methylated amine metabolites were increased. The deaminated 0-methylated metabolites were increased in the experiments with 3H-noradrenaline and decreased in the 3H-dopamine experiments. 3. Uptake of 3H-dopamine and 3H-noradrenaline by the hearts of 6-hydroxydopamine pretreated rats was decreased to a much smaller extent when perfused with the high concentration than with the low concentration. 4. At the high perfusion concentration there was a significant difference between control and pretreated animals with regard to the total radioactivity and the radioactivity in the alumina eluates only. The absolute and relative amounts of metabolites were not significantly changed by pretreatment with the exception of the deaminated catechol metabolites in the 3H-dopamine experiments. 5. It is concluded that neuronal Uptake 1 is greatly impaired in the hearts from rats pretreated with 6-hydroxydopamine, but extraneuronal Uptake 2 remains intact.

“…Systemically administered 6-hydroxydopamine (6-OHDA) produces a selective degeneration of adrenergic nerve terminals in peripheral sympathetically innervated organs Malmfors & Sachs, 1968). Catecholaminecontaining neurones in the rat brain appear to be similarly affected after the injection of 6-OHDA into the cerebrospinal fluid (Bloom, Algeri, Groppetti & Costa, 1969;Uretsky & Iversen, 1969, 1970Bartholini, Richards & Pletscher, 1970).…”

Section: Introductionmentioning

confidence: 99%

Time course of the effects of 6‐hydroxydopamine on catecholamine‐containing neurones in rat hypothalamus and striatum

Bell

Iversen

Uretsky

1970

Summary1. The effects of intraventricular injection of 6-hydroxydopamine (6-OHDA) on tyrosine hydroxylase activity, uptake of 3H-noradrenaline and endogenous catecholamine concentration in rat hypothalamus and striatum were investigated at various times after the injection of 6-OHDA. 2. In the hypothalamus after the injection of 250 Lg of 6-OHDA there was a rapid decrease in tyrosine hydroxylase activity, 3H-noradrenaline uptake and noradrenaline content, which was essentially complete within 2 hours. 3. In the striatum after this dose of 6-OHDA there was a much slower reduction in tyrosine hydroxylase activity and 3H-noradrenaline uptake during the first 48 h after drug injection. For the first 24 h the dopamine concentration in this brain area was increased significantly above control values, but had fallen below control values by 48 hours.4. After the injection of a smaller dose of 6-OHDA (25 ,tg) the only detectable change in the striatum was a rapid increase in the dopamine concentration. In the hypothalamus this dose induced a rapid depletion of noradrenaline, not accompanied initially by any significant reduction in tyrosine hydroxylase activity. 5. These results are consistent with the hypothesis that 6-OHDA causes a rapid degeneration of catecholamine-containing nerve terminals in the central nervous system (CNS). These degenerative changes, indicated by the loss of tyrosine hydroxylase and noradrenaline uptake sites, did not appear to be preceded by an initial displacement of endogenous catecholamines by 6-OHDA, except possibly at early times after the administration of small doses of the drug.