Experimental schizophrenia models in rodents established with inflammatory agents and cytokines.
Immune inflammatory processes in prenatal and perinatal stages are suggested to play crucial roles in the vulnerability to schizophrenia. Based upon this immune inflammatory hypothesis for schizophrenia, we have established animal models for this illness by subcutaneously administering cytokines or proinflammatory agents to rodent neonates. These models exhibit various schizophrenia-like behavioral abnormalities after puberty, most of which are sensitive to various antipsychotics. The experimental procedures are all simple and easily utilized by researchers unfamiliar with these models. The behavioral changes are reproducible and remarkable but do not accompany learning deficits. The molecular and cellular targets of these agents have also been investigated and partially characterized, such as the cortical GABAergic system, midbrain dopaminergic system and hippocampal glutamate system. In this chapter, we introduce the details of the procedure and discuss the potential application of these animal models to drug development for schizophrenia.
Division of Molecular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan. hnawa@bri.niigata-u.ac.jp
Hiroyuki
H
Nawa
Kiyofumi
K
Yamada
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016207:Cytokines / Q000494:pharmacology; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000494:pharmacology; D005260:Female; D059330:GABAergic Neurons / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced*; D018836:Inflammation Mediators / Q000494:pharmacology; D008636:Mesencephalon / Q000187:drug effects; D051379:Mice; D020890:Neuregulin-1 / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D012559:Schizophrenia / Q000139:chemically induced*
D016207:Cytokines; D018836:Inflammation Mediators; D020890:Neuregulin-1; D004815:Epidermal Growth Factor; D011070:Poly I-C