A novel biosensor with high signal-to-noise ratio for real-time measurement of dopamine levels in vivo.

Fast-scan cyclic voltammetry (FSCV) is an established method for measuring dopamine (DA) levels in the brain in real time. However, it is difficult to discriminate DA from other monoamines such as serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE). We report a novel DA-specific biosensor consisting of a carbon-fiber electrode coated with an ion-exchange membrane, a layer containing monoamine oxidase B, and a cellulose membrane. We performed FSCV using the probe to monitor the amount of DA in vitro and in vivo. First, we measured currents in vitro in phosphate-buffered saline as we added one micromole each of DA, 5-HT, and NE. The results confirmed that the biosensor selectively detected DA. Next, we implanted the probe in the striatum of male rats to investigate whether it could selectively detect changes in the DA content in vivo. The probe detected both the tonic change induced by methamphetamine administration and the phasic change induced by electrical stimulation of the medial forebrain bundle. In contrast, the electrode in the 6-hydroxydopamine-lesioned striatum did not respond to systemic selective serotonin or serotonin/norepinephrine reuptake inhibitors, confirming its selectivity. Furthermore, the probe in the striatum could still detect changes in the DA level 1 week after electrode implantation. The results suggest that the novel biosensor can measure real-time changes in DA levels in vivo with a relatively high signal-to-noise ratio.

Monosodium glutamate ingestion during the development period reduces aggression mediated by the vagus nerve in a rat model of attention deficit-hyperactivity disorder.

We used an umami substance, monosodium glutamate (MSG), as a simple stimulant to clarify the mechanism of the formation of emotional behavior. A 60 mM MSG solution was fed to spontaneously hypertensive rats (SHR), used as a model of attention-deficit hyperactivity disorder, from postnatal day 25 for 5 weeks kept in isolation. Emotional behaviors (anxiety and aggression) were then assessed by the open-field test, cylinder test and social interaction test. MSG ingestion during the developmental period resulted in a significant reduction in aggressive behavior but had few effects on anxiety-like behavior. Several experiments were performed to identify the reason for the reduced aggression with MSG intake. Blood pressure in the MSG-treated SHR was comparable to that of the controls during development. Argyrophil III staining to detect the very early phase of neuronal damage revealed no evidence of injury by MSG in aggression-related brain areas. Assessment of plasma amino acids revealed that glutamate levels remained constant (∼80 µM) with MSG ingestion, except for a transient increase after fasting (∼700 µM). However, lactate dehydrogenase assay in an in vitro blood-brain barrier model showed that cell toxicity was not induced by indirect MSG application even at 700 µM, confirming that MSG ingestion caused minimal neuronal damage. Finally, vagotomy at the sub-diaphragmatic level before MSG ingestion blocked its effect on aggressive behavior in the isolated SHR. The data suggest that MSG ingestion during the developmental period can reduce aggressive behavior in an attention deficit-hyperactivity disorder model rat, mediated by gut-brain interaction.