Use of Behavioral Analysis in Animal Models for Schizophrenia Research

Youngsik Woo; Saebom Lee; Jaehoon Jeong; Sang Ki Park

doi:10.16946/kjsr.2014.17.1.12

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Woo, Lee, Jeong, and Park: Use of Behavioral Analysis in Animal Models for Schizophrenia Research

Original Article

Korean J Schizophr Res 2014;17(1):12-26.

Published online: 20 January 2014

DOI: https://doi.org/10.16946/kjsr.2014.17.1.12

Use of Behavioral Analysis in Animal Models for Schizophrenia Research

Youngsik Woo, Saebom Lee, Jaehoon Jeong, Sang Ki Park

Department of Life Sciences, Pohang University of Science and Technology, Pohang, Korea

Address for correspondence: Sang Ki Park, Department of Life Sciences, Pohang University of Science and Technology, 77 Cheongam-Ro, Nam-Gu, Pohang 790-784, Korea Tel: 054-279-2349, Fax: 054-279-2199 E-mail: skpark@postach.ac.kr

Received 18 March 2014 Revised 31 March 2014 Accepted 2 April 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Animal models are useful tools to study the molecular basis of schizophrenia pathophysiology and efficacy of potential therapeutic agents. Schizophrenia animal models can be subdivided into three classes; drug-induced models, genetic models, and environmental models and each model is designed based on specific traits corresponding to the characteristic symptoms of human schizophrenia patients. Psychomotor agitation and sensitivity to psychotomimetic drugs are often thought to reflect positive symptoms. Social interaction deficits and affective impairments are known to correspond to negative symptoms. Also, cognitive symptoms have been linked to the working memory impairments, attention deficits and related cognitive deficits in animals. To analyze such components in quantifiable manners, various behavioral paradigms have been developed and utilized. Here, we overview these animal models, focusing on underlying rationales for their use in the context of schizophrenia research. (Korean J Schizophr Res 2014;17:12–26)

Keywords: Schizophrenia, Animal models, Animal behaviors, Behavioral tests.

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Table 1.

Overview of animal models linked to schizophrenia

	Models	Behavioral features
Pharmacological models	Gestational MAM model	Hyperactivity; deficits in PPI, set-shifting task, and social interaction
	PCP model	Hyperactivity; social isolation; deficits in PPI, cognitive functions, learning and memory
	Amphetamine model	Impaired PPI, attention, and set-shifting task
Genetic models	DISC1 model	Hyperactivity; PPI deficits; decreased spatial memory, spatial working memory, and social interaction
	NRG1 model	Hyperactivity; disrupted PPI, fear conditioning, mismatched negativity performance, and social interaction; increased aggression
	Dysbindin model	Increased amphetamine sensitivity and PPI; decreased working memory, spatial memory, novel object recognition, social contact during social interaction test
	Reelin model	Decreased locomotor activity; increased methamphetamine response; impaired PPI response, learning and memory, social activities
Environmental models	Prenatal immune challenge model	Increased psychotomimetic drug sensitivity; decreased social interaction, PPI, spatial memory, and fear conditioning response
Environmental models	Social stress model	Abnormal PPI response and object recognition test; increased anxious and aggressive behavior; anhedonia; avolition; hyperactivity

Table 2.

Symptoms of schizophrenia models and related behavioral tests in experimental animals

Symp	toms in human patients	Behavioral tests in animals	Behavioral features implicated in schizophrenia
Positive symptoms	Psychomotor agitation	Open field test	Increased locomotion in a novel environment
Positive symptoms	Sensitivity to psychotomimetic drugs	Open field test	Increased locomotor response to psychotic drugs
Negative symptoms	Social isolation/social withdrawal	Social interaction test Nesting behavior	Reduced hospitality to strangers Failure to build an intact nest
Negative symptoms	Depression/Anxiety disorders	Forced swim test Tail suspension test Elevated plus maze	Increased immobility in a cylinder Increased immobility Altered travelled distance and time spend in the open arms
Cognitive symptoms	Working memory impairment	Morris water maze T-maze	Increased time or failure to find hidden platform in the maze Frequent failures to make correct turns in the maze
		Fear conditioning	Disability to form fear memory with neutral stimulus
	Attention deficits	5-choice serial reaction time test	Reduced task accuracy and increased duration time to make correct decision
		Set-shifting task	Decreased cognitive flexibility to recognize and adapt to changed criteria
	Impaired sensorimotor gating	Prepulse inhibition	Impaired adaptation to sequential sensory stimulus

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