TY - JOUR
T1 - Prenatal methylazoxymethanol acetate alters behavior and brain NGF levels in young rats
T2 - A possible correlation with the development of schizophrenia-like deficits
AU - Fiore, Marco
AU - Talamini, Lucia
AU - Angelucci, Francesco
AU - Koch, Tineke
AU - Aloe, Luigi
AU - Korf, Jakob
PY - 1999/6/15
Y1 - 1999/6/15
N2 - It has been hypothesized that a deleterious key contribution to schizophrenia (SZ) development is a failure of migration and setting of young neurons into their appropriate cortical target sites, particularly in the entorhinal cortex (EC). To test this hypothesis in an animal model, we injected, in pregnant rats, on gestational day (GD) 9, or 10, or 11, or 12, the antimitotic compound methylazoxymethanolacetate (MAM) known to cause EC neuronal loss. We investigated whether or not EC disruption during prenatal development is able to affect behavior, including memory and learning, and brain nerve growth factor (NGF). Prenatally MAM treated young rats didn't display gross behavioral changes in social interaction, open-field and novel object investigation tests. By contrast, GD11 and GD12 MAM treated rats had a retardation in passive avoidance acquisition, while, in GD12 animals, pain sensitivity was reduced. GD12 animals also showed increased NGF in the EC and remaining cortex. MAM treated animals showed no changes in paw NGF or substance P levels suggesting that the altered nociceptive response is not related to local downregulation of these two molecules. The possibility that these behavioral and biochemical alterations might be associated with the onset of SZ is discussed. Copyright (C) 1999 Elsevier Science Ltd.
AB - It has been hypothesized that a deleterious key contribution to schizophrenia (SZ) development is a failure of migration and setting of young neurons into their appropriate cortical target sites, particularly in the entorhinal cortex (EC). To test this hypothesis in an animal model, we injected, in pregnant rats, on gestational day (GD) 9, or 10, or 11, or 12, the antimitotic compound methylazoxymethanolacetate (MAM) known to cause EC neuronal loss. We investigated whether or not EC disruption during prenatal development is able to affect behavior, including memory and learning, and brain nerve growth factor (NGF). Prenatally MAM treated young rats didn't display gross behavioral changes in social interaction, open-field and novel object investigation tests. By contrast, GD11 and GD12 MAM treated rats had a retardation in passive avoidance acquisition, while, in GD12 animals, pain sensitivity was reduced. GD12 animals also showed increased NGF in the EC and remaining cortex. MAM treated animals showed no changes in paw NGF or substance P levels suggesting that the altered nociceptive response is not related to local downregulation of these two molecules. The possibility that these behavioral and biochemical alterations might be associated with the onset of SZ is discussed. Copyright (C) 1999 Elsevier Science Ltd.
KW - Animal model
KW - Behavior
KW - Development
KW - Entorhinal cortex
KW - MAM
KW - NGF
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=0032921960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032921960&partnerID=8YFLogxK
U2 - 10.1016/S0028-3908(99)00007-6
DO - 10.1016/S0028-3908(99)00007-6
M3 - Article
C2 - 10465689
AN - SCOPUS:0032921960
VL - 38
SP - 857
EP - 869
JO - Neuropharmacology
JF - Neuropharmacology
SN - 0028-3908
IS - 6
ER -