Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice.
BACKGROUND
NG-nitro-L-arginine (L-NOARG), an inhibitor of nitric-oxide synthase (NOS), induces catalepsy in mice. This effect undergoes rapid tolerance, showing a significant decrease after 2 days of sub-chronic L-NOARG treatment. Nitric oxide (NO) has been shown to influence dopaminergic neurotransmission in the striatum. Neuroleptic drugs such as haloperidol, which block dopamine receptors, also cause catalepsy in rodents.


OBJECTIVE
To investigate the effects of subchronic L-NOARG treatment in haloperidol-induced catalepsy and the number of NOS neurons in areas related to motor control.


METHODS
Male albino Swiss mice were treated sub-chronically (twice a day for 4 days) with L-NOARG (40 mg/kg i.p.) or haloperidol (1 mg/kg i.p.). Catalepsy was evaluated at the beginning and the end of the treatments. Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry was also employed to visualize NOS as an index of enzyme expression in mice brain regions related to motor control.


RESULTS
L-NOARG sub-chronic administration produced tolerance of L-NOARG and of haloperidol-induced catalepsy. It also induced an increase in the number of NADPH-d-positive cells in the dorsal part of the caudate and accumbens nuclei compared with haloperidol and in the pedunculopontine tegmental nucleus compared with saline. In contrast, there was a decrease in NADPH-d neuron number in the substantia nigra, pars compacta in both haloperidol-treated and L-NOARG-treated animals.


CONCLUSIONS
The results give further support to the hypothesis that NO plays a role in motor behavior control and suggest that it may take part in the synaptic changes produced by antipsychotic treatment.
Del Bel
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EA
Department of Physiology, School of Odontology, FORP, Ribeirão Preto, SP, Brazil. eadelbel@usp.br
Guimarães
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FS
D000818:Animals; D002375:Catalepsy / Q000139:chemically induced*; D002452:Cell Count; D004298:Dopamine / Q000502:physiology; D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006220:Haloperidol; D006651:Histocytochemistry; D008297:Male; D051379:Mice; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology*; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D019335:Nitroarginine / Q000494:pharmacology
D018492:Dopamine Antagonists; D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496321:Nos1 protein, mouse; D009252:NADPH Dehydrogenase; D006220:Haloperidol; D004298:Dopamine