An Investigation of Hypofrontality in an Animal Model of Schizophrenia Using Real-Time Microelectrochemical Sensors for Glucose, Oxygen, and Nitric Oxide

作者：Finnerty Niall J; Bolger Fiachra B; Palsson Erik; Lowry John P^*

来源：ACS Chemical Neuroscience, 2013, 4(5): 825-831.

DOI：10.1021/cn4000567

• Hypofrontality
• brain
• electrochemical sensors
• real-time monitoring
• metabolism
• schizophrenia

Glucose, O-2, and nitric oxide (NO) were monitored in real time in the prefrontal cortex of freely moving animals using microelectrochemical sensors following phencyclidine (PCP) administration. Injection of saline controls produced a decrease in glucose and increases in both O-2 and NO. These changes were short-lived and typical of injection stress, lasting ca. 30 s for glucose and between 2 and 6 min for O-2 and NO, respectively. Subchronic PCP (10 mg/kg) resulted in increased motor activity and increases in all three analytes lasting several hours: O-2 and glucose were uncoupled with O-2 increasing rapidly following injection reaching a maximum of 70% (ca. 62 mu M) after ca. 15 min and then slowly returning to baseline over a period of ca. 3 h. The time course of changes in glucose and NO were similar; both signals increased gradually over the first hour post injection reaching maxima of 55% (ca. 982 mu M) and 8% (ca. 31 nM), respectively, and remaining elevated to within 1 h of returning to baseline levels (after ca. 5 and 7 h, respectively). While supporting increased utilization of glucose and O-2 and suggesting overcompensating supply mechanisms, this neurochemical data indicates a hyperfrontal effect following acute PCP administration which is potentially mediated by NO. It also confirms that long-term in vivo electrochemical sensors and data offer a real-time biochemical perspective of the underlying mechanisms.

• 出版日期2013-5