Effects of D-serine and atypical antipsychotics in neonatal ventral hippocampal damaged rats
| Project/Area Number |
16591149
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | Fukushima Medical University |
|---|
Principal Investigator |
NIWA Shinichi Fukushima Medical University, Department of Neuropsychiatry, School of Medicine, Professor (30110703)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | schizophrenia / neurodevelopmental disorder hypothesis of schizoph / rat models / neonatal ventral hippocampal damaged rat / D-serine / olanzapine / risperidone |
|---|
| Research Abstract |
Neonatal ventral hippocampal (nVH) damaged rat models, based on the neurodevelopmental disorder hypothesis of schizophrenia, have recently been shown to share many similarities with schizophrenia (e.g. susceptibility to stress, dopaminergic hypersensitivity, and postpubertal onset). We recently reported that this animal model showed hyperresponsiveness not only to methamphetamine (MAP) but also to phencyclidine (PCP), and this model does not depend on the extracellular concentration of dopamine in the nucleus accumbens, and glycine which acts as a co-agonist of N-methyl-D-aspartate (NMDA) receptor reduced MAP-induced hyperlocomotion in nVH damaged rats. From these findings, it is possible that this animal model may include the functional abnormalities both of dopaminergic-and of glutamatergic-systems after puberty, and the improvement of the glutamatergic dysfunction may have therapeutic effects. In the present study, we investigated whether the chronic treatment with D-serine, atypica
… More
l antipsychotics (risperidone: RIS, olanzapine: OLZ) and typical antipsychotic (haloperidol: HPD) reduce hyperactivity in adolescence. Each rats were treated with vehicle control or D-serine, RIS, OLZ, HPD, D-serine+RIS, D-serine+HPD for 28 days during PD56(in adolescence)-PD84, and were measured locomotor activity at PD70 and PD84. Hyperlocomotion of lesioned rats were suppressed by combination treatment of D-serine and antipsychotics than by monotherapy of D-serine or antipsychotics, and suppressive effect of antipsychotics combined with D-serine was higher in RIS-combined rats than in HPD. The novel finding of the present study was that the clonic treatment of antipsychotics combined with D-serine reduced nVH-induced hyperactivity (corresponding to positive symptoms of schizophrenia) in nVH damaged rats. These findings support the hypoglutamatergic hypothesis of schizophrenia, and raise the possibility that combination therapy of D-serine and antipsychotics could improve positive symptoms in patients with schizophrenia. Less
|
Report
(3 results)
Research Products
(11 results)
