Behavioral effects of intra-nigral microinjections of manganese chloride: Interaction with nitric oxide

Ponzoni, Silvia; Guimarães, Francisco Silveira; Bel, Elaine Aparecida Del; García-Cairasco, Norberto

doi:10.1016/s0278-5846(99)00090-1

Cited by 26 publications

(11 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This evidence may raise questions regarding which brain NO containing structure is mainly affected on Parkinson's disease. Our findings are in agreement with previous studies of our group (Ponzoni et al, 2000), showing an increase in CaudatePutamen NADPH-d neurons after lesion of Substantia Nigra compacta caused by manganese chloride. In this study, a protective role of NO was suggested since systemic L-NOARG treatment increased apomorphine-induced rotations.…”

Section: Nitric Oxide System and Experimental Parkinson'ssupporting

confidence: 94%

Role of Nitric Oxide on Motor Behavior

et al. 2005

View full text Add to dashboard Cite

The present review paper describes results indicating the influence of nitric oxide (NO) on motor control. Our last studies showed that systemic injections of low doses of inhibitors of NO synthase (NOS), the enzyme responsible for NO formation, induce anxiolytic effects in the elevated plus maze whereas higher doses decrease maze exploration. Also, NOS inhibitors decrease locomotion and rearing in an open field arena. These results may involve motor effects of this compounds, since inhibitors of NOS, NG-nitro-L-arginine (L-NOARG), N(G)-nitro-L-arginine methylester (L-NAME), N(G)-monomethyl-L-arginine (L-NMMA), and 7-Nitroindazole (7-NIO), induced catalepsy in mice. This effect was also found in rats after systemic, intracebroventricular or intrastriatal administration. Acute administration of L-NOARG has an additive cataleptic effect with haloperidol, a dopamine D2 antagonist. The catalepsy is also potentiated by WAY 100135 (5-HT1a receptor antagonist), ketanserin (5HT2a and alfal adrenergic receptor antagonist), and ritanserin (5-HT2a and 5HT2c receptor antagonist). Atropine sulfate and biperiden, antimuscarinic drugs, block L-NOARG-induced catalepsy in mice. L-NOARG subchronic administration in mice induces rapid tolerance (3 days) to its cataleptic effects. It also produces cross-tolerance to haloperidol-induced catalepsy. After subchronic L-NOARG treatment there is an increase in the density NADPH-d positive neurons in the dorsal part of nucleus caudate-putamen, nucleus accumbens, and tegmental pedunculupontinus nucleus. In contrast, this treatment decreases NADPH-d neuronal number in the substantia nigra compacta. Considering these results we suggest that (i) NO may modulate motor behavior, probably by interfering with dopaminergic, serotonergic, and cholinergic neurotransmission in the striatum; (ii) Subchronic NO synthesis inhibition induces plastic changes in NO-producing neurons in brain areas related to motor control and causes cross-tolerance to the cataleptic effect of haloperidol, raising the possibility that such treatments could decrease motor side effects associated with antipsychotic medications. Finally, recent studies using experimental Parkinson's disease models suggest an interaction between NO system and neurodegenerative processes in the nigrostriatal pathway. It provides evidence of a protective role of NO. Together, our results indicate that NO may be a key participant on physiological and pathophysiological processes in the nigrostriatal system.

show abstract

Section: Nitric Oxide System and Experimental Parkinson'ssupporting

confidence: 94%

Role of Nitric Oxide on Motor Behavior

et al. 2005

View full text Add to dashboard Cite

show abstract

“…For example, in the striatum in Parkinsonian animal models and humans, NOS has been described as either depressed (rodents – De-Vente et al, 2000; Barthwal et al, 2001; Sancesario et al, 2004; humans – Böckelmann et al, 1994; Eve et al, 1998) or increased (rodents – Ponzoni et al, 2000; Gomes and Del Bel, 2003; Gomes et al, 2008; humans – Hunot et al, 1996; Eve et al, 1998). Additionally, in the 6-OHDA-lesioned striatum, a considerable population of medium spiny neurons presented an excitatory response induced by the NO donor 3-morpholinosydonimine (SIN-1; Di Giovanni et al, 2003; Galati et al, 2008) instead of the inhibition observed in non-lesioned animals.…”

Section: Introductionmentioning

confidence: 99%

Nitric Oxide Synthase Inhibitor Improves De Novo and Long-Term l-DOPA-Induced Dyskinesia in Hemiparkinsonian Rats

Padovan-Neto¹,

Echeverry²,

Chiavegatto³

et al. 2011

Front. Syst. Neurosci.

View full text Add to dashboard Cite

Inhibitors of neuronal and endothelial nitric oxide synthase decrease l-3,4-dihidroxifenilalanine (l-DOPA)-induced dyskinesias in rodents. The mechanism of nitric oxide inhibitor action is unknown. The aims of the present study were to investigate the decrease of l-DOPA-induced abnormal involuntary movements (AIMs) in 6-hydroxydopamine (6-OHDA)-lesioned rats by nitric oxide inhibitors following either acute or chronic treatment. The primary findings of this study were that NG-nitro-l-Arginine, an inhibitor of endothelial and neuronal nitric oxide synthase, attenuated AIMs induced by chronic and acute l-DOPA. In contrast, rotational behavior was attenuated only after chronic l-DOPA. The 6-OHDA lesion and the l-DOPA treatment induced a bilateral increase (1.5 times) in the neuronal nitric oxide synthase (nNOS) protein and nNOS mRNA in the striatum and in the frontal cortex. There was a parallel increase, bilaterally, of the FosB/ΔFosB, primarily in the ipsilateral striatum. The exception was in the contralateral striatum and the ipsilateral frontal cortex, where chronic l-DOPA treatment induced an increase of approximately 10 times the nNOS mRNA. Our results provided further evidence of an anti-dyskinetic effect of NOS inhibitor. The effect appeared under l-DOPA acute and chronic treatment. The l-DOPA treatment also revealed an over-expression of the neuronal NOS in the frontal cortex and striatum. Our results corroborated findings that l-DOPA-induced rotation differs between acute and chronic treatment. The effect of the NOS inhibitor conceivably relied on the l-DOPA structural modifications in the Parkinsonian brain. Taken together, these data provided a rationale for further evaluation of NOS inhibitors in the treatment of l-DOPA-induced dyskinesia.

show abstract

“…In rodents exposed experimentally to Mn, the morphological changes resemble those in human Parkinson's disease [Ponzoni et al, 2000]. The Mn-induced neurological manifestations indicate a significant relationship with dopaminergic [Hirata et al, 2001] and cholinergic [Pappas et al, 1997] regulation of certain other neurotransmitters (glutamate, GABA, acetylcholine, norepinephrine; Trepper et al [1998]).…”

Section: Introductionmentioning

confidence: 99%