Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats

Novaretti, Nathália; Padovan-Neto, Fernando E.; Tumas, Vítor; da-Silva, C.A.; Bel, Elaine Aparecida Del

doi:10.1590/s0100-879x2010007500111

Cited by 16 publications

(16 citation statements)

References 38 publications

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“…L-DOPA increased nNOS mRNA levels in the contra-and ipsilateral side to the DA lesion of the frontal cortex [193] but did not produce any further increases of nNOS protein in the striatum compared to the 6-OHDA-induced increase [193]. 7-NI and L-NOARG treatment prevented dyskinesia-induced by L-DOPA [179,186,193] and 7-NI improved motor performance in rats [179,186]. Especially noteworthy is also the evidence that 7-NI sub-chronic administration was devoid of tolerance to the anti-dyskinetic effect [179] differently from its cataleptic action [64], effects on SNc DA cell-population electrophysiological activity and DA striatal release [47].…”

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 74%

“…7-NI and L-NOARG treatment prevented dyskinesia-induced by L-DOPA [179,186,193] and 7-NI improved motor performance in rats [179,186]. Especially noteworthy is also the evidence that 7-NI sub-chronic administration was devoid of tolerance to the anti-dyskinetic effect [179] differently from its cataleptic action [64], effects on SNc DA cell-population electrophysiological activity and DA striatal release [47]. The hypothesis that raises NO/GC/cGMP pathway activity in the CNS is also supported by some evidence in Parkinsonian patients.…”

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 86%

“…The latter hypothesis is centred on the increased activity of cholinergic interneurons in DA-lesioned striatum that might facilitate the activity of specific subclass of MSNs [175] by the activation of different subtypes of muscarinic receptors. In other words, parkinsonian state is associated with an abnormal NOergic activity that may also contribute to the pathogenesis of L-DOPAinduced dyskinesias (LID) [176][177][178][179].…”

Section: No Implication On Bg Dysfunctionmentioning

confidence: 99%

“…Promising neurotransmitter targets are the noradrenergic, serotonergic, GLUergic, and adenosinergic systems [181,185]. Recently, some evidence has been also produced in both animal models and in PD patients suggesting a contributory role of NO signalling in LID [178,179,[186][187][188][189]. Hitherto, the study of NO in the effects of L-DOPA has produced conflicting results.…”

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 99%

“…Recently, more compelling evidence that an over-activity of NO system could contribute to the pathogenesis of LID has been obtained by using rodent-models of the disease [178,179,186,187]. For example, chronic L-DOPA treatment induced FosB expression in the striatum D1 MSNs and in NOS-positive striatal interneurons in rodent PD-models [178,193].…”

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 99%

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Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

Pierucci

Galati

Valentino

et al. 2011

CNSNDDT

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Several recent studies have emphasized a crucial role for the nitrergic system in movement control and the pathophysiology of the basal ganglia (BG). These observations are supported by anatomical evidence demonstrating the presence of nitric oxide synthase (NOS) in all the basal ganglia nuclei. In fact, nitrergic terminals have been reported to make synaptic contacts with both substantia nigra dopamine-containing neurons and their terminal areas such as the striatum, the globus pallidus and the subthalamus. These brain areas contain a high expression of nitric oxide (NO)-producing neurons, with the striatum having the greatest number, together with important NO afferent input. In this paper, the distribution of NO in the BG nuclei will be described. Furthermore, evidence demonstrating the nitrergic control of BG activity will be reviewed. The new avenues that the increasing knowledge of NO in motor control has opened for exploring the pathophysiology and pharmacology of Parkinson's disease and other movement disorders will be discussed. For example, inhibition of striatal NO/guanosine monophosphate signal pathway by phosphodiesterases seems to be effective in levodopa-induced dyskinesia. However, the results of experimental studies have to be interpreted with caution given the complexities of nitrergic signalling and the limitations of animal models. Nevertheless, the NO system represents a promising pharmacological intervention for treating Parkinson's disease and related disorders.

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Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 74%

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 86%

Section: No Implication On Bg Dysfunctionmentioning

confidence: 99%

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 99%

Section: Role Of No In L-dopa-induced Dyskinesiamentioning

confidence: 99%

See 3 more Smart Citations

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

Pierucci

Galati

Valentino

et al. 2011

CNSNDDT

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Dopaminergic Neurons in Parkinson’s Disease

Prediger

Bortolanza

Issy

et al. 2014

Handbook of Neurotoxicity

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Counteraction by Nitric Oxide Synthase Inhibitor of Neurochemical Alterations of Dopaminergic System in 6-OHDA-Lesioned Rats Under l-DOPA Treatment

et al. 2013

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Nitric oxide synthase inhibitors reduce L-3, (Del-Bel et al., Cell Mol Neurobiol 25(2):371-392, 2005) 4-dihydroxyphenylalanine (L-DOPA)-induced abnormal motor effects subsequent to depletion of dopaminergic neurons in rodents and non-human primates. The present study used quantitative high-performance liquid chromatography to analyze, for the first time, dopamine metabolism in striatum of rats in order to elucidate the mechanism of action of the nitric oxide synthase inhibitors. Adult male Wistar rats received unilateral microinjection of saline (sham) or 6-hydroxydopamine (6-OHDA-lesioned) in the medial forebrain bundle. Past 3 weeks, rats were treated during 21 days with L-DOPA/benserazide (30 mg/kg/7.5 mg/kg, respectively, daily). On the 22nd day rats received an intraperitoneal (i.p.) injection of either vehicle or 7-nitroindazole, a preferential neuronal nitric oxide synthase inhibitor before L-DOPA. Abnormal involuntary movements and rotarod test were assessed as behavioral correlate of motor responses. Lesion intensity was evaluated through tyrosine hydroxylase immunohystochemical reaction. Dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), and an extent of dopamine striatal tissue levels/dopamine metabolism were measured in the striatum. Lesion with 6-OHDA decreased dopamine, DOPAC, and DOPAC/dopamine ratio in the lesioned striatum. L-DOPA treatment induced abnormal involuntary movements and increased DOPAC/dopamine ratio (nearly five times) in the lesioned striatum. L-DOPA-induced dyskinesia was mitigated by 7-nitroindazole, which also decreased dopamine turnover, dopamine and DOPAC levels. Our results revealed an almost two times increase in dopamine content in the non-lesioned striatum of 6-OHDA-lesioned rats. Reduction of striatal DOPAC/dopamine ratio in dyskinetic rats may suggest an increase in the dopamine availability. Our data confirm contribution of nitrergic transmission in the pathogenesis of L-DOPA-induced dyskinesia with potential utilization of nitric oxide synthase inhibitors for treatment.

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Lack of tolerance for the anti-dyskinetic effects of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in rats

Cited by 16 publications

References 38 publications

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

Nitric Oxide Modulation of the Basal Ganglia Circuitry: Therapeutic Implication for Parkinson's Disease and Other Motor Disorders

Dopaminergic Neurons in Parkinson’s Disease

Counteraction by Nitric Oxide Synthase Inhibitor of Neurochemical Alterations of Dopaminergic System in 6-OHDA-Lesioned Rats Under l-DOPA Treatment

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