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Nitric oxide synthase inhibitors improve prepulse inhibition responses of Wistar rats

Issy, A.C. ; Lazzarini, M. ; Szawka, R.E. ; Carolino, R.O.G. ; Anselmo-Franci, J.A. ; Del Bel, E.A.

Behavioural brain research, 2011-03, Vol.217 (2), p.416-423 [Periódico revisado por pares]

Shannon: Elsevier B.V

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Título:
Nitric oxide synthase inhibitors improve prepulse inhibition responses of Wistar rats
Autor: Issy, A.C. ; Lazzarini, M. ; Szawka, R.E. ; Carolino, R.O.G. ; Anselmo-Franci, J.A. ; Del Bel, E.A.
Assuntos: Acoustic Stimulation - adverse effects ; Analysis of Variance ; Animals ; Anticonvulsants - pharmacology ; Antipsychotics ; Behavior, Animal - drug effects ; Behavioral psychophysiology ; Biogenic Monoamines - metabolism ; Biological and medical sciences ; Brain - drug effects ; Brain - metabolism ; Diazepam - pharmacology ; Dopamine Antagonists - pharmacology ; Dose-Response Relationship, Drug ; Drug Interactions ; Enzyme Inhibitors - pharmacology ; Exploratory Behavior - drug effects ; Fundamental and applied biological sciences. Psychology ; Haloperidol - pharmacology ; Indazoles - pharmacology ; Inhibition (Psychology) ; Male ; Medical sciences ; Neuropharmacology ; Nitric oxide ; Nitric Oxide Synthase - antagonists & inhibitors ; Nitric Oxide Synthase - metabolism ; Nitroarginine - pharmacology ; NOS inhibitors ; Pharmacology. Drug treatments ; Prepulse inhibition ; Psycholeptics: tranquillizer, neuroleptic ; Psychology. Psychoanalysis. Psychiatry ; Psychology. Psychophysiology ; Psychopharmacology ; Rat ; Rats ; Rats, Wistar ; Reflex, Startle - drug effects ; Spontaneous prepulse inhibition disruption
É parte de: Behavioural brain research, 2011-03, Vol.217 (2), p.416-423
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Descrição: ▶ Antipsychotics and nitric oxide inhibitors increase PPI on Wistar rats with low PPI responses. ▶ Lower PPI phenotype may be driven by an overactive catecholamine system. ▶ Probably, there is a dopamine and nitric oxide interaction on PPI modulation. ▶ Lower PPI phenotype may represent a non-pharmacological model to evaluate new antipsychotics. Cognitive and attentional deficits in schizophrenia include impairment of the sensorimotor filter as measured by prepulse inhibition (PPI). In this way, the study of animals that naturally present low PPI responses could be a useful approach for screening new antipsychotic drugs. Several pieces of evidence suggest that dopamine and nitric oxide (NO) can modulate PPI but their role in those animals is unknown. The aim of this study was to investigate the role of dopamine and NO in Wistar rats with naturally low PPI response. Male Wistar rats with low PPI responses received an i.p. injection of the antipsychotics haloperidol (0.1, 0.3 or 1mg/kg) or clozapine (0.5, 1.5 or 5mg/kg), the anxiolytic diazepam (1 or 3mg/kg) or the NO synthase (NOS) inhibitors, NG- nitro-l-arginine (l-NOARG; 40mg/kg, acutely or sub-chronically) or 7-Nitroindazole (7-NI; 3, 10 or 30mg/kg). All animals were submitted to the PPI test 1h after injection. Striatal and cortical dopamine, DOPAC, and noradrenaline levels of rats with low PPI responses were compared to rats with normal PPI responses. We found increased levels of catecholamines on the striatum and prefrontal cortex of Wistar rats with low PPI. In these animals, both antipsychotics, typical and atypical, and NOS inhibitors significantly increased PPI. Taken together, our findings suggest that the low PPI phenotype may be driven by an overactive catecholamine system. Additionally, our results corroborate the hypothesis of dopamine and NO interaction on PPI modulation and suggest that Wistar rats with low PPI may represent an interesting non-pharmacological model to evaluate new potential antipsychotics.
Editor: Shannon: Elsevier B.V
Idioma: Inglês

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Nitric oxide synthase inhibitors improve prepulse inhibition responses of Wistar rats

Issy, A.C. ; Lazzarini, M. ; Szawka, R.E. ; Carolino, R.O.G. ; Anselmo-Franci, J.A. ; Del Bel, E.A.

Shannon: Elsevier B.V

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