Sustained brain-derived neurotrophic factor up-regulation and sensorimotor gating abnormality induced by postnatal exposure to phencyclidine: comparison with adult treatment
Article first published online: 26 JUL 2006
Journal of Neurochemistry
Volume 99, Issue 3, pages 770–780, November 2006
How to Cite
Takahashi, M., Kakita, A., Futamura, T., Watanabe, Y., Mizuno, M., Sakimura, K., Castren, E., Nabeshima, T., Someya, T. and Nawa, H. (2006), Sustained brain-derived neurotrophic factor up-regulation and sensorimotor gating abnormality induced by postnatal exposure to phencyclidine: comparison with adult treatment. Journal of Neurochemistry, 99: 770–780. doi: 10.1111/j.1471-4159.2006.04106.x
- Issue published online: 8 AUG 2006
- Article first published online: 26 JUL 2006
- Received February 23, 2006; revised manuscript received June 19, 2006; accepted June 24, 2006.
- limbic system;
- prepulse inhibition;
Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression and the behavioral effects. Both single and repeated phencyclidine injections into adult rats induced BDNF up-regulation in the corticolimbic system and a decrease in prepulse inhibition, both of which were transient. In contrast, subchronic postnatal administration increased BDNF protein and mRNA levels in the hippocampus and entorhinal cortex, which were sustained until 8 weeks of age. In parallel, the postnatal rats treated with phencyclidine developed a persistent decrease in prepulse inhibition at the adult stage. The chronic BDNF increase appeared to contribute to the prepulse inhibition abnormality, as subchronic BDNF infusion into the hippocampus of normal rats mimicked the prepulse inhibition deficits. This study suggests that phencyclidine exposure during brain development induces sustained BDNF up-regulation in the limbic system with a biological link to sensorimotor gating deficits.