Korean J Psychopharmacol.  2006 May;17(3):291-301.

Effects of Quetiapine on the Immobilization Stress-induced BDNF and CRF Expression in Rat Brain

• Park SW
• Lee SK
• Kim YK
• Lee SJ
• Joo MJ
• Rhee CG
• Kim YH

Abstract

OBJECTIVE
In this study we examined the effects of quetiapine on the immobilization stress-induced brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRF) expression in rat brain. We also assessed the antidepressant activity of quetiapine. METHOD: We used in situ hybridization to examine the effects of chronic administration of quetiapine in gene transcription. This study also examined the influence of quetiapine in an animal model of depression, the forced swimming test (FST).
RESULTS
1) Repeated immobilization stress (2 hr daily for 3 weeks) decreased mRNA levels of BDNF in the hippocampus (p<0.01), parietal cortex (p<0.01) and pyriform cortex (p<0.05). 2) Repeated immobilization stress increased mRNA levels of CRF in the hypothalamic paraventricular nucleus (PVN)(p<0.01). 3) Chronic quetiapine (10 mg/kg) treatment (daily for 3 weeks) alone significantly increased BDNF mRNA expression in the dentate gyrus of hippocampus when compared to controls under basal conditions (p<0.01), whereas no such effect was observed in the neocortex. 4) Chronic pretreatment of quetiapine also markedly increased the stress-induced decrease of BDNF mRNA expression in the hippocampus (p<0.01) and neocortex (p<0.01). 5) Moreover, the stress-induced elevation of CRF mRNA expression was blocked by chronic quetiapine pretreatment in PVN (p<0.01) although chronic quetiapine treatment alone did not significantly reduce CRF mRNA levels in comparison to controls under basal condition. 6) When rats received acutely quetiapine, quetiapine did reduce the immobility time at 10 mg/kg, as compared with the control group (p<0.05).
CONCLUSION
: These results suggest that quetiapine has not only potentially an antidepressant effect but also a neuroprotective action in schizophrenia and this effect may be related to its antipsychotic effect in patients with schizophrenia.

Keyword

Quetiapine; Schizophrenia; Brain-derived neurotrophic factor; Corticotropin-releasing factor; Antidepressant; Forced swimming test; Immobilization stress; Hippocampus

MeSH Terms

Animals
Antipsychotic Agents
Brain*
Brain-Derived Neurotrophic Factor*
Corticotropin-Releasing Hormone
Dentate Gyrus
Depression
Hippocampus
Humans
Immobilization*
In Situ Hybridization
Models, Animal
Neocortex
Paraventricular Hypothalamic Nucleus
Physical Exertion
Rabeprazole
Rats*
RNA, Messenger
Schizophrenia
Quetiapine Fumarate
Antipsychotic Agents
Brain-Derived Neurotrophic Factor
Corticotropin-Releasing Hormone
RNA, Messenger