Chronic treatment with I‐dopa plus carbidopa in hemitransected rats: Preferential effects at intact dopamine synapses leading to behavioural signs of dopamine receptor supersensitivity

Agnati, Luigi F.; Fuxé, Kjell; Calzà, Laura; Zini, Isabella; Benefenati, Fabio; Farabegoli, C.; Goldstein, Menek

doi:10.1111/j.1748-1716.1983.tb07236.x

Cited by 18 publications

(1 citation statement)

References 21 publications

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“…The lesion cuts ascending and descending pathways including the nigrostriatal dopaminergic system with the exception of its most medial components (Agnati et al, 1983). As controls sham-operated rats were used (four rats).…”

Section: Methodsmentioning

confidence: 99%

Localization of thioredoxin in the rat brain and functional implications

et al. 1995

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The immunoreactivity for thioredoxin, which catalyzes protein disulfide reductions, has previously been shown to exist in nerve cells and their axons. Here we demonstrate the localization of thioredoxin mRNA as revealed by in situ hybridization in the rat brain. The gene is expressed in nerve cells of a variety of brain regions, for example, the cerebral cortex, the piriform cortex, the medial preoptic area, the CA3/CA4 region of the hippocampal formation, the dentate gyrus, the paraventricular nucleus of the hypothalamus, the arcuate nucleus, the substantia nigra pars compacta, the locus coeruleus, the ependyma of the 4th ventricle, and the epithelial cells of the choroid plexus. This distribution implicates an important function in nerve cell metabolism, especially in regions with high energy demands and indicates a role of the choroid plexus in nerve cell protection from environmental influences. It was found that after mechanical injury induced by partial unilateral hemitransection the thioredoxin mRNA expression is upregulated in the lesioned area and spreads to the cortical hemispheres at the lesioned level. This induction suggests a function of thioredoxin in the regeneration machinery of the brain following mechanical injury and oxidative stress.

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Section: Methodsmentioning

confidence: 99%

Localization of thioredoxin in the rat brain and functional implications

et al. 1995

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Chronic levodopa impairs the recovery of dopamine agonist-induced rotational behavior following neural grafting

et al. 1991

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The effect of chronic levodopa treatment on the function of embryonic mesencephalic tissue grafts was assessed in rats by monitoring rotational behavior elicited by dopamine (DA) agonists before and after neural grafting. Rats were given unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal pathway and baseline measures of rotational behavior induced by D1 receptor stimulation, D2 receptor stimulation, or amphetamine were determined. Subsequently, DA grafts were implanted into the lesioned striatum and chronic regimens of either saline or levodopa began one day after neural grafting and were continued for 7 weeks. Rotational behavior elicited by the D1 agonist, SKF 38393, was completely attenuated throughout the six-week-period following the commencement of levodopa treatment, regardless of the absence or presence of a DA graft. Conversely, rotational behavior elicited by the D2 agonist, quinpirole, was significantly elevated in ungrafted animals receiving chronic levodopa. Grafted animals receiving chronic levodopa did not show a significant reduction in rotational behavior, whereas grafted animals receiving chronic saline showed a significant 67% reduction in quinpirole-induced rotational behavior. Amphetamine-induced rotational behavior was reduced in both levodopa and saline treated grafted animals, however grafted animals receiving chronic levodopa treatment showed a reduction of rotational behavior that was uncharacteristic and less compensatory than that observed in grafted animals receiving chronic saline treatment. Morphology of grafts indicate that there were areas of impaired neurite outgrowth of TH-positive fibers in animals treated with levodopa. The results of the present study suggest that the impaired recovery in quinpirole- and amphetamine-induced rotational behavior in grafted animals receiving chronic levodopa treatment may be related to (1) impaired graft function, (2) an alteration in pre- and postsynaptic mechanisms in the host DAergic system, or (3) a combined effect of (1) and (2).

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The comparative long-term effects of ciladopa (AY-27,110), a chemically novel dopaminergic agonist, in 6-OHDA-lesioned and intact rats

Voith

1985

Psychopharmacology

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The effect of the chemically novel dopaminergic agonist, ciladopa (AY-27,110) was studied on rotational behavior in unilaterally 6-OHDA-lesioned rats and on stereotyped behavior in normal animals during and after chronic treatment. Ciladopa, at a 1.25 mg/kg SC daily dose, was administered for 4 and 6 weeks to the lesioned and normal animals, respectively. This dose was threshold for turning but subthreshold with respect to stereotypy. Both behaviors were evaluated weekly during chronic treatment and biweekly for 11 weeks after its discontinuation in response to doses previously shown to elicit turning and stereotypy. The chronic administration of ciladopa enhanced rotational behavior considerably more and with an earlier onset than stereotypy, although the duration of behavioral supersensitivity after cessation of treatment was the same. These results indicate that behaviors mediated by supersensitive or intact dopamine receptors are differently affected by chronic dopamine agonist treatment. The results are discussed in relation to their potential therapeutic implications and current concepts of agonist-induced supersensitivity.

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Chronic treatment with I‐dopa plus carbidopa in hemitransected rats: Preferential effects at intact dopamine synapses leading to behavioural signs of dopamine receptor supersensitivity

Cited by 18 publications

References 21 publications

Localization of thioredoxin in the rat brain and functional implications

Localization of thioredoxin in the rat brain and functional implications

Chronic levodopa impairs the recovery of dopamine agonist-induced rotational behavior following neural grafting

The comparative long-term effects of ciladopa (AY-27,110), a chemically novel dopaminergic agonist, in 6-OHDA-lesioned and intact rats

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