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

Rationale: N-G-nitro-L-arginine (L-NOARG), an inhibitor of nitric-oxide syn thase (NOS), induces catalepsy in mice. This effect undergoes rapid toleran ce, showing a significant decrease after 2 days of sub-chronic L-NOARG trea tment. Nitric oxide (NO) has been shown to influence dopaminergic neurotran smission in the striatum. Neuroleptic drugs such as haloperidol, which bloc k dopamine receptors, also cause catalepsy in rodents. Objectives: To inves tigate the effects of subchronic L-NOARG treatment in haloperidol-induced c atalepsy and the number of NOS neurons in areas related to motor control. M ethods: Male albino Swiss mice were treated sub-chronically (twice a day fo r 4 days) with L-NOARG (40 mg/kg i.p.) or haloperidol (1 mg/kg i.p.). Catal epsy was evaluated at the beginning and the end of the treatments. Reduced nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemi stry 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 cat alepsy. 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 halop eridol and in the pedunculopontine tegmental nucleus compared with saline. In contrast, there was a decrease in NADPH-d neuron number in the substanti a nigra, pars compacta in both haloperidol-treated and L-NOARG-treated anim als. Conclusions: The results give further support to the hypothesis that N O plays a role in motor behavior control and suggest that it may take part in the synaptic changes produced by antipsychotic treatment.