2003 Fiscal Year Final Research Report Summary
Prepulse inhibition and prevertion of disease in a putative animal model of schizophrenia
| Project/Area Number |
12670931
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Psychiatric science
|
|---|
| Research Institution | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
|---|
Principal Investigator |
TSUNODA Masahiko Toyama Medical and Pharmaceutical University, University Hospital, Neuropsychiatry, Assistant, 附属病院, 助手 (30322762)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Michio Toyama Medical and Pharmaceutical University, Faculty of Medicine, Neuropsychiatry, Assistant professor, 医学部, 助教授 (40236013)
SUMIYOSHI Tomiki Toyama Medical and Pharmaceutical University, University Hospital, Neuropsychiatry, Lectureer, 附属病院, 講師 (80286062)
UEHARA Takashi Toyama Medical and Pharmaceutical University, Faculty of Medicine, Neuropsychiatry, Assistant, 医学部, 助手 (70303229)
|
|---|
| Project Period (FY) |
2000 – 2003
|
| Keywords | prepulse inhibition / entorhinal cortex / isolation / antipsychotics / animal model / schizophrenia / social interaction / phencyclidine |
|---|
| Research Abstract |
Prepulse inhibition(PPI) deficits have been shown in rats through neuroanatomical or environmental manipulation. The aim of this study was to determine whether unilateral entorhinal cortical(EC) lesions and/or isolation-housing influence the PPI of acoustic startle in adolescent rats. We also investigated the acute effects of haloperidol or clozapine on the disruption of PPI in the EC lesioned rats. Quinolinic acid (lesion operation) or phosphate buffered saline (sham operation) was infused into the unilateral EC of adolescent (postnatal 7 weeks) male Wistar rats. After operation, the rats were housed individually or pair-housed, thus yielding lesion/isolation, lesion/pair, sham/isolation, and sham/pair groups. On the 28th postoperative day, the rats with the unilateral lesions exhibited attenuation of PPI compared with that of the sham-operated rats. Moreover, the left lesion/isolation rats demonstrated a significantly greater decrease in PPI compared with the left lesion/pair rats, w
… More
hile this effect of isolation was not found in the right-lesioned rats. Both haloperidol and clozapine reversed the disruption of PPI in the left or right EC lesioned rats. These findings suggest that left EC lesions may enhance the ability of environmental stress to produce disturbances in sensorimotor gating, and that the disruption of PPI in EC lesioned rats may be dependent on altered dopamine (DA) transmissions. Furthermore, we measured DA-related behaviors and methamphetamine (MAP)-induced DA release in the accumbens (NAC) nucleus in these animals. The lesioned rats exhibited significantly greater spontaneous or MAP (1mg/kg, i.p.)-induced locomotor activity on the 14th and 28th postoperative day. MAP-induced DA release in NAC was measured by in vivo microdialysis on the 28th postoperative day. Lesioned rats did not show a significant change in MAP-induced DA release in NAC compared to sham-operated animals. These results suggest that excitotoxic damage of the left EC produces behavioral changes consistent with alterd mesolimbic dopaminergic transmissions, possibly mediated by postsynaptic supersesitivity.
Animals treated with phencyclidine (PCP) are thought animal models of schizophrenia. Arginine vasopressin(AVP) is a peptide involved in social behaviors in rodents. To iinvestigate the mechanism underlying the deficits in social behavior induced by blockade of N-methyl-D-aspartate (NMDA) receptors, this study examined the effect of PCP on AVP receptor binding and social interaction in the rats. Subchronic PCP administration (2mg/kg/day, 14 days, i.p.) significantly reduced the density of V1a reveptor binding sites, labeled by an [125i]-linear AVP antagonist, in several brain regions. Subchronic treatment with PCP impaired social interactions in rats, as has been previously reported. These results suggest that NMDA antagonists have modulatory effects on the central vasopressinergic system and social interaction. Less
|
