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Dopamine and nitric oxide interaction on the modulation of prepulse inhibition of the acoustic startle response in the Wistar rat

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Abstract

Rationale

The nitric oxide (NO)–arginine pathway is intimately connected to the release of dopamine (DA), a neurotransmitter system that may be dysfunctional in schizophrenia. Both schizophrenic patients and rats treated with DA agonists present deficits in sensorimotor gating measured by prepulse inhibition (PPI).

Objective

Our aim was to investigate the interaction between a NO synthase inhibitor, N G-nitro-l-arginine (l-NOARG), and the DA agonists, amphetamine (Amph), apomorphine (Apo), bromocriptine (BRC), quinpirole (QNP) and SKF38393, on the modulation of the PPI.

Methods

Male Wistar rats received two injections of either l-NOARG (40 mg/kg, i.p.) or saline, 1 h before the test, and the DA agonists or vehicle. Testing began 5 min after treatment with Amph (2 mg/kg, i.p.), Apo (0.5 mg/kg, s.c.) or QNP (0.3 mg/kg and 1.0 mg/kg, s.c.), 120 min after BRC (1 and 40 mg/kg, i.p.) and 15 min after SKF38393 (10 mg/kg, s.c.). The PPI test consisted of 60 presentations divided into pulse (100 dB), prepulse (65, 70, 75 and/or 80 dB) and prepulse + pulse.

Results

l-NOARG prevented the PPI disruption caused by Amph (2 mg/kg). Apo, QNP and BRC disrupted PPI, but these effects were not significantly changed by l-NOARG. SKF38393 had no significant effect on PPI whether or not preceded by l-NOARG.

Conclusions

Our findings show that l-NOARG interacted with Amph, an indirect DA agonist, but not with the direct DA agonists on PPI, suggesting that NO is involved on the dopaminergic modulation of sensorimotor gating, probably by a presynaptic mechanism.

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Acknowledgement

We would like to thank Célia Aparecida da-Silva for technical support. This research was supported by FAPESP, CNPq, CAPES, Brazil.

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Authors and Affiliations

  1. Department of Physiology, FORP, University of São Paulo, Av. Café S/N, 14040-904, Ribeirão Preto, SP, Brazil

    C. Salum & E. A. Del Bel

  2. Department of MEF-Physiology, FORP, Campus USP, Av. Café S/N, 14040-904, Ribeirão Preto, SP, Brazil

    C. Salum

  3. Department of Pharmacology, FMRP, University of São Paulo, Av. Bandeirantes 13400, 14049-900, Ribeirão Preto, SP, Brazil

    F. S. Guimarães

  4. Laboratory of Psychobiology, University of São Paulo, Av. Bandeirantes 13400, 14049-900, Ribeirão Preto, SP, Brazil

    M. L. Brandão

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  1. C. Salum
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  4. E. A. Del Bel
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Correspondence to C. Salum.

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Salum, C., Guimarães, F.S., Brandão, M.L. et al. Dopamine and nitric oxide interaction on the modulation of prepulse inhibition of the acoustic startle response in the Wistar rat. Psychopharmacology 185, 133–141 (2006). https://doi.org/10.1007/s00213-005-0277-z

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