title: An augmented dopamine system function is present prior to puberty in the methylazoxymethanol acetate rodent model of schizophrenia.
abstract: Schizophrenia is a disease typically associated with an adolescent onset. Although there have been a considerable number of imaging studies investigating the transition to psychosis in prodromal patients, there are relatively few preclinical studies examining potential mechanisms that may contribute to adolescent onset. We have previously demonstrated, in the methylazoxymethanol acetate (MAM) rodent model of schizophrenia, that an enhanced activity within the ventral hippocampus may underlie the dopamine system hyperfunction, suggested to contribute to positive symptoms in patients. Here we demonstrate that the aberrant regulation of dopamine system function, in MAM-treated rats, is present prior to puberty. Furthermore, we now report that while the afferent regulation of ventral tegmental area dopamine neurons (from the hippocampus and pedunculopontine tegmental area) appears intact in preadolescent rats, the behavioral response to alterations in dopamine system function appears to be attenuated in preadolescent rats. Thus, we posit that the pathological alterations underlying psychosis may be present prior to symptom onset and that the "normal" development of the postsynaptic side of the dopamine system may underlie the transition to psychosis.
authors.affiliation: Department of Pharmacology & Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio, San Antonio, Texas; Department of Physiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China; Department of Pathophysiology, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Perez
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lodge
mesh_terms: D000200:Action Potentials; D000661:Amphetamine / Q000008:administration & dosage; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage; D059290:Dopaminergic Neurons / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000254:growth & development* / Q000503:physiopathology*; D008746:Methylazoxymethanol Acetate; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000254:growth & development / Q000503:physiopathology; D010320:Parvalbumins / Q000378:metabolism; D045042:Pedunculopontine Tegmental Nucleus / Q000254:growth & development / Q000503:physiopathology*; D017207:Rats, Sprague-Dawley; D012559:Schizophrenia / Q000503:physiopathology*; D012741:Sexual Maturation; D017557:Ventral Tegmental Area / Q000254:growth & development / Q000503:physiopathology*
chemical_list: D015259:Dopamine Agents; D010320:Parvalbumins; D008746:Methylazoxymethanol Acetate; D000661:Amphetamine; D004298:Dopamine
keywords: MAM rat; hippocampus; parvalbumin; preadolescent; schizophrenia