Potential beneficial effects of caffeine administration in the neonatal period of an animal model of schizophrenia

Author(s)

Ramos, Aline Camargo ^[1] ; Hungria, Filipe de Mattos ^{[1, 2]} ; Camerini, Bianca Avansi ^{[1, 2]} ; Suiama, Mayra Akimi ^[3] ; Calzavara, Mariana Bendlin ^{[1, 4, 2]}

Affiliation

^[1] Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, SP - Brazil

^[2] Calzavara, Mariana Bendlin, Fac Israelita Ciencias Saude Albert Einstein, Sch Med, Sao Paulo, SP, Brazil.Ramos, Aline Camargo, Univ Fed Sao Paulo, Dept Psychiat, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Dept Pharmacol, Sao Paulo, SP - Brazil

^[4] Fac Israelita Ciencias Saude Albert Einstein, Sch Med, Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: Behavioural Brain Research; v. 391, AUG 5 2020.
• Web of Science Citations: 0

Abstract

Obstetric complications, like maternal hypertension and neonatal hypoxia, disrupt brain development, leading to psychiatry disorders later in life, like schizophrenia. The exact mechanisms behind this risk are not yet well known. Spontaneously hypertensive rats (SHR) are a well-established model to study neurodevelopment of schizophrenia since they exhibit behavioral alterations mimicking schizophrenia that can be improved with antipsychotic drugs. SHR mothers are hypertensive, and the SHR offspring develop in preeclampsia-like conditions. Hypoxic conditions increase levels of adenosine, which play an important role in brain development. The enhanced levels of adenosine at birth could be related to the future development of schizophrenia. To investigate this hypothesis adenosine levels of brain neonatal Wistar rats and SHR were quantified. After that, caffeine, an antagonist of adenosinergic system, was administrated on PND (postnatal day) 7 (neurodevelopmental age similar to a human at delivery) and rats were observed at adolescent and adult ages. We also investigated the acute effects of caffeine at adolescent and adult ages. SHR control adolescent and adult groups presented behavioral deficits like hyperlocomotion, deficit in social interaction (SI), and contextual fear conditioning (CFC). In SHR, neonatal caffeine treatment on PND 7 normalized hyperlocomotion, improved SI, and CFC observed at adolescent period and adult ages, showing a beneficial effect on schizophrenia-like behaviors. Wistar rats neonatally treated with caffeine exhibited hyperlocomotion, deficit in SI and CFC when observed at adolescent and adult ages. Acutely caffeine treatment administrated at adolescent and adult ages increased locomotion and decreased SI time of Wistar rats and impair CFC in adult Wistars. No effects were observed in SHR. In conclusion, caffeine can be suggested as a useful drug to prevent behavioral deficits observed in this animal model of prenatal hypoxia-induced schizophrenia profile when specifically administered on PND 7. (AU)

• FAPESP's process: 15/26820-0 - EVALUATION OF EFFECTS OF NEONATAL HYPOXIA ON SCHIZOPHRENIA DEVELOPMENT: ROLE OF ADENOSINERGIC SYSTEM
• Grantee: Aline Camargo Ramos
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/19972-3 - Effects of neonatal hypoxia on the development of schizophrenia: role of the adenosinergic system
• Grantee: Mariana Bendlin Calzavara
• Support type: Regular Research Grants
• FAPESP's process: 14/06961-5 - Effects of adenosinergic agonists and antagonists on the emotional, social and preattentional processes in an animal model of schizophrenia
• Grantee: Mariana Bendlin Calzavara
• Support type: Regular Research Grants