, Volume 147, Issue 4, pp 356-361

Sub-chronic inhibition of nitric-oxide synthesis modifies haloperidol-induced catalepsy and the number of NADPH-diaphorase neurons in mice

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Rationale: N G-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. Objectives: To investigate the effects of sub-chronic 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.

Received: 23 February 1999 / Final version: 28 July 1999