Sustained brain-derived neurotrophic factor up-regulation and sensorimotor gating abnormality induced by postnatal exposure to phencyclidine: comparison with adult treatment.
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.
Takahashi
Makoto
M
Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Kakita
Akiyoshi
A
Futamura
Takashi
T
Watanabe
Yuichiro
Y
Mizuno
Makoto
M
Sakimura
Kenji
K
Castren
Eero
E
Nabeshima
Toshitaka
T
Someya
Toshiyuki
T
Nawa
Hiroyuki
H
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D015152:Blotting, Northern; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis* / Q000494:pharmacology / Q000502:physiology*; D006213:Hallucinogens / Q000494:pharmacology*; D006624:Hippocampus; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008845:Microinjections; D010622:Phencyclidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D013216:Reflex, Startle / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D006213:Hallucinogens; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine