Abstract
In the present study, we investigated the involvement of prefrontal glutamatergic neurotransmission in the enhancement of immobility (emotional deficit) in a forced swimming test in mice treated with phencyclidine (PCP: 10 mg/kg/day for 14 days) repeatedly, which is regarded as an animal model for negative symptoms. A decrease in spontaneous extracellular glutamate release and increase in levels of the glutamate transporter GLAST, were observed in the prefrontal cortex (PFC) of PCP-treated mice, compared to saline-treated mice. NMDA receptor subunit 1 (NR1) and Ca2+/calmoduline kinase II (CaMKII) were markedly activated in the PFC of saline-treated mice, but not PCP-treated mice, immediately after the forced swimming test. The facilitation of the function of NMDA receptors by d-cycloserine (30 mg/kg i.p.), an NMDA receptor glycine-site partial agonist, reversed the enhancement of immobility in the forced swimming test and impairment of CaMKII activation in the PCP-treated mice. Microinjection of dl-threo-β-benzyloxyaspartate (10 nmol/site/bilaterally), a potent blocker of glutamate transporters, into the PFC of PCP-treated mice also had an attenuating effect. In addition, activation of glial cells and a decrease of neuronal cell size were observed in the PFC of PCP-treated mice. These results suggest that repeated PCP treatment disrupts pre- and post-synaptic glutamatergic neurotransmission and induces morphological changes in the PFC and that such changes cause the emotional deficits exhibited in PCP-treated mice.
| Original language | English |
|---|---|
| Pages (from-to) | 152-160 |
| Number of pages | 9 |
| Journal | Behavioural Brain Research |
| Volume | 180 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 18-06-2007 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Behavioral Neuroscience
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Hypofunctional glutamatergic neurotransmission in the prefrontal cortex is involved in the emotional deficit induced by repeated treatment with phencyclidine in mice : Implications for abnormalities of glutamate release and NMDA-CaMKII signaling. / Murai, Rina; Noda, Yukihiro; Matsui, Kanae; Kamei, Hiroyuki; Mouri, Akihiro; Matsuba, Kazuhisa; Nitta, Astumi; Furukawa, Hiroshi; Nabeshima, Toshitaka.
In: Behavioural Brain Research, Vol. 180, No. 2, 18.06.2007, p. 152-160.Research output: Contribution to journal › Article
TY - JOUR
T1 - Hypofunctional glutamatergic neurotransmission in the prefrontal cortex is involved in the emotional deficit induced by repeated treatment with phencyclidine in mice
T2 - Implications for abnormalities of glutamate release and NMDA-CaMKII signaling
AU - Murai, Rina
AU - Noda, Yukihiro
AU - Matsui, Kanae
AU - Kamei, Hiroyuki
AU - Mouri, Akihiro
AU - Matsuba, Kazuhisa
AU - Nitta, Astumi
AU - Furukawa, Hiroshi
AU - Nabeshima, Toshitaka
PY - 2007/6/18
Y1 - 2007/6/18
N2 - In the present study, we investigated the involvement of prefrontal glutamatergic neurotransmission in the enhancement of immobility (emotional deficit) in a forced swimming test in mice treated with phencyclidine (PCP: 10 mg/kg/day for 14 days) repeatedly, which is regarded as an animal model for negative symptoms. A decrease in spontaneous extracellular glutamate release and increase in levels of the glutamate transporter GLAST, were observed in the prefrontal cortex (PFC) of PCP-treated mice, compared to saline-treated mice. NMDA receptor subunit 1 (NR1) and Ca2+/calmoduline kinase II (CaMKII) were markedly activated in the PFC of saline-treated mice, but not PCP-treated mice, immediately after the forced swimming test. The facilitation of the function of NMDA receptors by d-cycloserine (30 mg/kg i.p.), an NMDA receptor glycine-site partial agonist, reversed the enhancement of immobility in the forced swimming test and impairment of CaMKII activation in the PCP-treated mice. Microinjection of dl-threo-β-benzyloxyaspartate (10 nmol/site/bilaterally), a potent blocker of glutamate transporters, into the PFC of PCP-treated mice also had an attenuating effect. In addition, activation of glial cells and a decrease of neuronal cell size were observed in the PFC of PCP-treated mice. These results suggest that repeated PCP treatment disrupts pre- and post-synaptic glutamatergic neurotransmission and induces morphological changes in the PFC and that such changes cause the emotional deficits exhibited in PCP-treated mice.
AB - In the present study, we investigated the involvement of prefrontal glutamatergic neurotransmission in the enhancement of immobility (emotional deficit) in a forced swimming test in mice treated with phencyclidine (PCP: 10 mg/kg/day for 14 days) repeatedly, which is regarded as an animal model for negative symptoms. A decrease in spontaneous extracellular glutamate release and increase in levels of the glutamate transporter GLAST, were observed in the prefrontal cortex (PFC) of PCP-treated mice, compared to saline-treated mice. NMDA receptor subunit 1 (NR1) and Ca2+/calmoduline kinase II (CaMKII) were markedly activated in the PFC of saline-treated mice, but not PCP-treated mice, immediately after the forced swimming test. The facilitation of the function of NMDA receptors by d-cycloserine (30 mg/kg i.p.), an NMDA receptor glycine-site partial agonist, reversed the enhancement of immobility in the forced swimming test and impairment of CaMKII activation in the PCP-treated mice. Microinjection of dl-threo-β-benzyloxyaspartate (10 nmol/site/bilaterally), a potent blocker of glutamate transporters, into the PFC of PCP-treated mice also had an attenuating effect. In addition, activation of glial cells and a decrease of neuronal cell size were observed in the PFC of PCP-treated mice. These results suggest that repeated PCP treatment disrupts pre- and post-synaptic glutamatergic neurotransmission and induces morphological changes in the PFC and that such changes cause the emotional deficits exhibited in PCP-treated mice.
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UR - http://www.scopus.com/inward/citedby.url?scp=34248183019&partnerID=8YFLogxK
U2 - 10.1016/j.bbr.2007.03.003
DO - 10.1016/j.bbr.2007.03.003
M3 - Article
VL - 180
SP - 152
EP - 160
JO - Behavioural Brain Research
JF - Behavioural Brain Research
SN - 0166-4328
IS - 2
ER -