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

I The concentrations of p-and m-tyramine were measured in the caudate nucleus of the rat brain following subcutaneous injection of reserpine or intraventricular injection of 6-hydroxydopamine. fPhenylethylamine was analysed in the hypothalamus after reserpine.2 Endogenous levels ofp-tyramine and m-tyramine in the caudate nucleus, andp-phenylethylamine in the hypothalamus were 8.02, 2.25 and 2.52 ng/g respectively. 3 Tyramine concentrations were reduced to less than 20% of control values one day after a reserpine injection of 1 or 10 mg/kg. A single dose of reserpine (0.4 mg/kg) significantly decreased the content of both tyramines in the caudate nucleus. The effects became apparent as early as 45 min after drug administration and persisted for at least 6 h in the case of p-tyramine and for at least 19 days in the case of m-tyramine.4 The hypothalamic content of P-phenylethylamine was unaffected by reserpine. 5Ten days after an intraventricular injection of 6-hydroxydopamine (250 1tg), p-and m-tyramine concentrations in the caudate nucleus were significantly below control levels. 6 The results suggest that p-and m-tyramine may be stored by an intraneuronal reserpine-sensitive storage mechanism. Alternatively, the tyramines may replace some of the catecholamines from their storage granules and then be released as false transmitters by the nervous impulse. The observed changes in tyramine levels might also reflect the fact that these amines may be metabolically related to another amine which is stored in reserpine-sensitive granules.

Section: Introductionmentioning

confidence: 99%

The Effects of Reserpine and 6‐hydroxydopamine on the Concentrations of Some Arylalkylamines in Rat Brain

Boulton

Juorio

Philips

et al. 1977

“…No ptosis was observed and catalepsy was present only in those animals receiving higher doses (25 and 50 ,ug icv). All animals showed a decrease in locomotor activity compared with controls, an observation previously made in the rat by Laverty & Taylor (1970). …”

Section: Effect On the Antinociceptive Activity Of Morphinementioning

confidence: 88%

Pharmacological properties of centrally‐administered agents which interfere with neurotransmitter function: a comparison with the central depressant effects of ouabain

Doggett

Spencer

1973

Summary1. Centrally administered sodium diethyldithiocarbamate (DDC) produced hypothermia, central nervous depression and potentiation of the antinociceptive effect of morphine. These effects resemble those seen with centrally administered ouabain. Furthermore, the interactions of (+)-amphetamine, desmethylimipramine and nialamide with DDC and ouabain were similar. 2. 6-Hydroxydopamine by the same route also produced central nervous depressant effects including hypothermia, decreased locomotor activity and catalepsy but not ptosis. 3. Both ouabain and chlorpromazine produced similar effects on behaviour and body temperature including selective abolition of a conditioned avoidance response.4. Although centrally administered tetrabenazine produced ptosis, decreased locomotor activity and catalepsy, it had no significant effect on body temperature. However, the hypothermia produced by peripherally administered reserpine was reversed by centrally administered dibutyryl cyclic 3',5'-adenosine monophosphate. 5. Centrally administered cocaine and desmethylimipramine produced no depressant effects but an increased excitability and responsiveness were apparent in both cases. 6. Although the observed behavioural depression and hypothermia can occur independently both seem to involve an interference with dopaminergic systems.

“…Laverty et al, 1965;Malmfors & Sachs, 1968;Tranzer & Thoenen, 1968) and in the central nervous system (e.g. Uretsky & Iversen, 1969;Laverty & Taylor, 1970). This action is secondary to displacement of endogenous NA and appears to be due to intraaxonal oxidation of 6-OHDA, with consequent production of free radicals and mitochondrial damage (Kostrzewa & Jacobowitz, 1974;Silvka & Cohen, 1985).…”

Section: Discussionmentioning

confidence: 99%

Effects on renal sympathetic axons in dog of acute 6‐hydroxydopamine treatment in combination with selective neuronal uptake inhibitors

Sunn

Harris

Bell

1990

1 In anaesthetized dogs, we have investigated the effect on renal responses to sympathetic nerve stimulation of acute treatment with the catecholaminergic neurotoxin 6-hydroxydopamine (2 mg kg-1 i.v.), administered alone or after blockade of neuronal catecholamine uptake pathways for noradrenaline (NA) or dopamine with desmethylimipramine or benztropine, respectively. 2 Under control conditions, renal nerve stimulation caused renal vasoconstriction, reduced glomerular filtration and sodium and water excretion and caused net efflux of NA and dopamine into the renal venous plasma. Two h after administration of 6-hydroxydopamine alone, there was abolition of both functional responses and catecholamine efflux during nerve stimulation. 3 In animals pretreated with desmethylimipramine (1 mgkg-), 6-hydroxydopamine had no significant effect on functional responses to renal nerve stimulation and nerve-evoked efflux of NA was only moderately reduced. Efflux of dopamine was still markedly reduced by 6-hydroxydopamine, but more variably than occurred without desmethylimipramine treatment. 4 In animals pretreated with benztropine (0.2mg kg-1), nerve-evoked efflux of dopamine, but not that of NA, was protected against reduction by 6-hydroxydopamine. A higher dose of benztropine (1 mg kg 1) protected efflux of both NA and dopamine against 6-hydroxydopamine. 5 We conclude that acute treatment with a low dose of 6-hydroxydopamine is an effective method of inactivating peripheral sympathetic nerves. The differential effects of desmethylimipramine and benztropine in preserving nerve-evoked efflux of NA and dopamine after 6-hydroxydopamine support the view that these catecholamines originate predominantly from different intrarenal axons. However, neither uptake blocker appears to be completely specific in its actions.