The role of striatum and prefrontal cortex in the prevention of amphetamine-induced schizophrenia-like effects mediated by nitric oxide compounds

Autor(es)

Issy, Ana Carolina ^{[1, 2]} ; dos-Santos-Pereira, Mauricio ^{[1, 2, 3]} ; Cordeiro Pedrazzi, Joao Francisco ^{[2, 4]} ; Cussa Kubrusly, Regina Celia ^[5] ; Del-Bel, Elaine ^{[1, 2, 3, 4]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dent Sch Ribeirao Preto, Dept Morphol Physiol & Basic Pathol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Physiol, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Med Sch Ribeirao Preto, Dept Neurosci & Behav Sci, Ribeirao Preto, SP - Brazil

^[5] Univ Fed Fluminense, Dept Physiol & Pharmacol, Biomed Inst, Niteroi, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 86, p. 353-362, AUG 30 2018.
• Citações Web of Science: 2

Resumo

Pharmacological manipulation of nitric oxide (NO) has been suggested as a promising treatment for schizophrenia symptoms. A single infusion of sodium nitroprusside, a NO donor with short half-life, was found to improve schizophrenia symptoms. However, an increasing number of preclinical studies have demonstrated the potential beneficial effects of both NO donors and inhibitors. We investigated the potential synergistic effect of sub-effective doses of the NO donor sodium nitroprusside or the NO inhibitor 7-Nitroindazole (7NI) combined with clozapine, a standard atypical antipsychotic, on counteracting amphetamine or MK-801-induced psychosis-like behaviors. The impact of sodium nitroprusside and 7NI on cAMP regulation in the prefrontal cortex and striatum was also evaluated. Confirming previous results, we found that both NO donors and inhibitors prevented amphetamine-induced effects (prepulse inhibition {[}PPI] disruption and hyperlocomotion). In addition, we observed a synergistic effect of sodium nitroprusside and clozapine on antagonizing the disruptive effects of amphetamine, but not MK-801, in the PPI test. The sub-effective dose of 7NI tested did not prevent amphetamine or MK-induced PPI effects when combined with clozapine. Interestingly, cAMP levels were significantly decreased in the prefrontal cortex after treatment with sodium nitroprusside. In the striatum, both sodium nitroprusside and 7NI blocked the amphetamine-induced increase of cAMP. Our data corroborate previous findings on the dopaminergic mechanisms involved in the action of sodium nitroprusside. It is likely that the differential effects of sodium nitroprusside are related to its ability to modify cAMP levels in the prefrontal cortex. (AU)

• Processo FAPESP: 12/17626-7 - Mecanismos celulares e moleculares envolvidos no papel de neurotransmissores atípicos em transtornos neuropsiquiátricos
• Beneficiário: Francisco Silveira Guimaraes
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/11449-3 - Vias de Sinalização e Estruturas Encefálicas Envolvidas na Interação Óxido Nítrico/Dopamina no Filtro Sensório-Motor
• Beneficiário: Ana Carolina de Castro Issy Pereira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado