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Psychiatric Disorders in Animal Models of Schizophrenia

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Handbook of Neurotoxicity

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Abstract

Schizophrenia is a devastating mental illness in which characteristic symptoms appear, including “positive” (i.e., hallucinations and delusions), “negative” (i.e., anhedonia, lack of motivation, and social withdrawal), and cognitive symptoms (i.e., memory and cognitive deficits). The causes of schizophrenia are still unknown. The dopaminergic hypothesis suggests that hyperfunction of the mesolimbic dopamine system is the cause of the appearance of “positive” symptoms of schizophrenia. In contrast, the glutamatergic hypothesis focuses on the hypofunction of the NMDA receptor, which is preferentially expressed on GABAergic interneurons in cortical regions. To date, there is no effective treatment for schizophrenia that would eliminate all the symptoms characteristic of this disease. 1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) is an endogenous compound that is found in plants as well as in mammalian brains. 1MeTIQ affects a number of neurotransmitter systems (e.g., dopaminergic, serotonergic, noradrenergic, and glutamatergic) in the brain by modulating their activity. This compound exhibits a number of beneficial effects, including neuroprotective, antiaddictive, and antidepressant-like properties. Moreover, 1MeTIQ has shown anxiolytic properties in the elevated plus maze (EPM) test and demonstrated pro-cognitive effects in the novel object recognition (NOR) test in a ketamine model of schizophrenia. The antipsychotic potential of 1MeTIQ is similar to that of olanzapine, which is an antipsychotic drug. However, in the prepulse inhibition test (PPI), which is a model of the negative symptoms of schizophrenia, 1MeTIQ did not inhibit the MK-801-induced memory impairment or sensorimotor gating deficits. In conclusion, 1MeTIQ will be useful as a drug to reduce positive but not negative symptoms of schizophrenia.

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Abbreviations

1H MRS:

Proton magnetic resonance spectroscopy

1MeTIQ:

1-Methyl-1,2,3,4-tetrahydroisoquinoline

3-MT:

3-Methoxytyramine

5-HT:

Serotonin

CPu:

Caudate putamen

EPM:

Elevated plus maze test

GABA:

gamma-Aminobutyric acid

GAD:

Glutamate decarboxylase

MAM:

Methylazoxymethanol acetate

MK-801:

Dizocilpine

mPFC:

Medial prefrontal cortex

MS:

Maternal separation

MSNs:

Medium spiny neurons

NAS:

Nucleus accumbens

NMDA:

N-methyl-D-aspartate

NOR:

Novel object recognition test

PCP:

Phencyclidine

PEA:

Phenylethylamine

PET:

Positron-emission tomography

PLC:

Prelimbic cortex

PPI:

Prepulse inhibition test

ROS:

Reactive oxygen species

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Acknowledgement

This study was financially supported through a grant from the National Science Centre Grant No. 2017/25/B/NZ7/01096 and statutory funds from the Maj Institute of Pharmacology, Polish Academy of Sciences, Krakow, Poland.

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  1. Department of Neurochemistry, Maj Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland

    Agnieszka Wąsik

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  1. Agnieszka Wąsik
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Correspondence to Agnieszka Wąsik .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA

    Richard M. Kostrzewa

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Wąsik, A. (2021). Psychiatric Disorders in Animal Models of Schizophrenia. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_241-1

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