Understanding translational research in schizophrenia: A novel insight into animal models

Abstract

Schizophrenia affects millions of people worldwide and is a major challenge for the scientific community. Like most psychotic diseases, it is also considered a complicated mental disorder caused by an imbalance in neurotransmitters. Due to the complexity of neuropathology, it is always a complicated disorder. The lack of proper understanding of the pathophysiology makes the disorder unmanageable in clinical settings. However, due to recent advances in animal models, we hope we can have better therapeutic approaches with more success in clinical settings. Dopamine, glutamate, GABA, and serotonin are the neurotransmitters involved in the pathophysiology of schizophrenia. Various animal models have been put forward based on these neurotransmitters, including pharmacological, neurodevelopmental, and genetic models. Polymorphism of genes such as dysbindin, DICS1, and NRG1 has also been reported in schizophrenia. Hypothesis based on dopamine, glutamate, and serotonin are considered successful models of schizophrenia on which drug therapies have been designed to date. New targets like the orexin system, muscarinic and nicotinic receptors, and cannabinoid receptors have been approached to alleviate the negative and cognitive symptoms. The non-pharmacological models like the post-weaning social isolation model (maternal deprivation), the isolation rearing model etc. have been also developed to mimic the symptoms of schizophrenia and to create and test new approaches of drug therapy which is a breakthrough at present in psychiatric disorders. Different behavioral tests have been evaluated in these specific models. This review will highlight the currently available animal models and behavioral tests in psychic disorders concerning schizophrenia.

Keywords: Animal models; Animal models of schizophrenia; Psychotic diseases; Schizophrenia; Schizophrenia models.

Fig. 1

A Pathophysiology of schizophrenia according to dopamine hypothesis, B Depicts amphetamine associated morphological and behavioral changes in mesolimbic pathway of brain, C Depicts behavioral changes and pathways associated with NVHL, D depicts prenatal stress model

Fig. 2

A Depicts the causes and effects produced by PWSI and further how to suppress it B Depicts the experimental setup and steps involved in isolation rearing mode C Depicts different approaches to induce prenatal immune challenges D Depicts prenatal exposure of polyriboinosinic-polyribocytidylic acid (Poly-I:C) on 9th and 17th gestational day generates positive and negative/cognitive symptoms respectively of the disorder E Depicts the different nutritional deficiency leading to abnormalities in neurotransmitters and neurotransmission F represents interaction of dysbindin with different proteins