, 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

  • E.A. Del Bel
  • F. S. Guimarães
Original Investigation

DOI: 10.1007/s002130050003

Cite this article as:
Del Bel, E. & Guimarães, F. Psychopharmacology (2000) 147: 356. doi:10.1007/s002130050003


Rationale: 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. 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.

Key words Nitric oxidel-NOARGHaloperidolDopamineCatalepsyToleranceNADPH-diaphorase

Copyright information

© Springer-Verlag Berlin Heidelberg 2000

Authors and Affiliations

  • E.A. Del Bel
    • 1
  • F. S. Guimarães
    • 2
  1. 1.Department of Physiology, School of Odontology, FORP, Campus USP, Av. Café S/No, 14040-904, Ribeirão Preto, SP, Brazil e-mail:, Tel.: +55-16-6024047, Fax: +55-16-6332301BR
  2. 2.Department of Pharmacology, School of Medicine, Campus USP, Av. Café S/No, 14040-904, Ribeirão Preto, SP, BrazilBR