Estudo do efeito antipsicótico do óleo essencial de Alpinia zerumbet em comparação ao antipsicótico atípico olanzapina em modelo experiental de esquizofrenia

Abstract

Schizophrenia is a chronic psychiatric disorder characterized by the presence of positive, negative and cognitive symptoms. A widely used animal model involves repeated administration of ketamine (TEC) that induces the disease symptoms as well as causes oxidative damage. The Alpinia zerumbet is a plant whose essential oil (OEAZ) has shown important antipsychotic effect in previous studies of our research group. Based on this statement the present study aimed to determine the effects of OEAZ in the prevention and reversal of positive symptoms (pre-pulse inhibition test -PPI), negative (social interaction -SI) and cognitive (maze Y) induced by repeated administration of CET and to assess neurochemical changes as part of its mechanism of action: Reduced Glutathione - (GSH); Nitrite (indirect measurement of nitric oxide); Levels of brain-derived neurotrophic factor (BDNF); Interleukin-6 (IL-6) and to study the possible adversities related to the oil effect, extrapyramidal events (catalepsy), changes in body weight (BW). For the prevention protocol, male mice were pretreated with OEAZ 100 and 200 mg / kg (OEAZ 100 and OEAZ 200) or Olanzapine 2 mg / kg (OLANZA) or saline (SAL) for 7 days, from 8 ° to 14 ° CET was added. The reversal protocol the animals were pretreated with CET the 1st to the 7th day and 8 ° to 14 ° OEAZ 100 and 200 or OLANZA or SAL were added. CET caused deficit in the IPP, social interaction and the Labyrinth Y, reduced GSH levels, nitrite and BDNF, and increased IL-6. The CET has reduced immobility in catalepsy and increased PC of animals. The OEAZ 100 was able to prevent the PPI deficits caused, SI and Maze Y. OEAZ 200 increased the time SI. In reversing the OEAZ 100 and 200 increased the index in PPI and Y maze. OLANZA improved the index in the PPI, SI. 100 OEAZ prevented by increasing GSH levels in the CPF (prefrontal cortex) and CE (striatum) and did not alter the HC (hippocampus) in reversal, increased the CPF, HC, EC. The OEAZ 200 was not significant in preventing, but reverted low GSH levels in all three areas. In nitrite levels OEAZ 100 and 200 is not prevented, but reversed increasing the HC and CE Regarding BDNF only OEAZ 100 and OLANZA were able to increase the levels in the prevention and reversal, the Olaza only reversed. Both doses of OEAZ and OLANZA significantly reduced IL-6 levels. In the evaluation of possible side effects OEAZ 100 and 200 slightly increased immobility time of animals. On Pc OLANZA increased sharply, while the OEAZ 100 and 200 increased and reduced respectively in preventing and acted contrary to the reversal. Overall the OEAZ presented a similar performance to antipsychotic, preventing and reversing the positive, negative and cognitive symptoms. Its mechanism involves dopaminergic pathways, neurotrophic and antioxidants.