Toru Misaki

Clonidine reduces dopamine and increases GABA in the nucleus accumbens: an in vivo microdialysis study.

The effects of clonidine, an alpha2 adrenoceptor agonist, on extracellular concentrations of dopamine and gamma-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied by using in vivo brain microdialysis. Clonidine (5 microg/kg i.v.) significantly decreased the brain microdialysate concentration of dopamine in the nucleus accumbens up to a maximum of 16% at its peak effect. This effect was inhibited by a dose of idazoxan (10 microg/kg i.v.), an alpha2-adrenoceptor antagonist. which itself did not affect the efflux of dopamine. A smaller dose of clonidine (1 microg/kg i.v.), which had no significant effect on dopamine efflux per se, decreased the dopamine efflux (21% reduction) when given together with an ineffective dose of midazolam (0.075 mg/kg i.v.), a benzodiazepine receptor agonist. The effect of clonidine (5 microg/kg i.v.) on mesolimbic dopamine efflux was abolished by bicuculline (1 mg/kg i.v.), a GABA(A) receptor antagonist, counteracted by beta-carboline-3-carboxylate ethyl ester (beta-CCE, 3 mg/kg i.p.), a benzodiazepine receptor inverse agonist, but not affected by flumazenil (6 microg/kg i.v.), a benzodiazepine receptor antagonist. Clonidine (5 microg/kg i.v.) increased the dialysate concentration of GABA in the nucleus accumbens up to a maximum of 250% at its peak effect, but not in the ventral tegmental area. It is hypothesized that GABA(A) binding sites in the nucleus accumbens form part of the sequence of events that is triggered by clonidine in an alpha2-adrenergic-specific manner and that ultimately results in a decreased release of dopamine in the nucleus accumbens.

Transient in vivo membrane depolarization and glutamate release before anoxic depolarization in rat striatum

Increased extracellular glutamate ([GLU]e), under the condition of cerebral ischemia, anoxia or hypoxia, has been recognized as being associated with neuronal cell damage and death. We performed real-time monitoring of [GLU]e dynamics in vivo in the rat striatum during systemic acute anoxia or hypoxia, as well as monitoring the direct current potential (DC) and cerebral blood flow (CBF). Adult Wistar rats were orotracheally intubated and artificially ventilated with room air. A microdialysis electrode, temperature sensor probe, DC microelectrode and laser Doppler probe were then implanted. The inspired gas was changed to 100% N(2) (anoxia), or to 3, 5 or 8% O(2) (remainder N(2)) (hypoxia). With 100% N(2), distinct biphasic [GLU]e elevations were observed. With 3% O(2), a transient [GLU]e increase was seen before anoxic depolarization (AD). With 5% O(2), however, the start of the transient [GLU]e increase was significantly delayed. Anoxia-induced depolarization started at about 100 s. The 3% O(2)-induced transient depolarization and AD began at nearly the same time as the transient and AD-induced increase in [GLU]e. Similarly, the responses to 5% O(2) showed significant delays in the transient depolarization and AD-induced increase in [GLU]e. CBF during 3 or 5% O(2) hypoxic insult was consistently maintained above the control level, i.e., prior to cardiac arrest. Our new dialysis electrode method employing both GOX and ferrocene-conjugated bovine serum albumin allowed evaluation of transient [GLU]e dynamics in the early phase of severe hypoxia in vivo.

Influence of blood pressure on cardio-ankle vascular index (CAVI) examined based on percentage change during general anesthesia

Cardio-ankle vascular index (CAVI) and brachial-ankle pulse wave velocity (baPWV) are non-invasive methods for estimating arterial distensibility. The purpose of this study is to evaluate whether CAVI as an index of true arterial stiffness is superior to baPWV based on the percentage change in hemodynamics under general anesthesia. CAVI (segment from heart to ankle), k-CAVI (heart to knee) and baPWV (brachial to ankle) in 30 oral surgery patients were measured to compare the decreased blood pressure (BP) after 10 min of tracheal intubation during general anesthesia with the control BP (after 5 min of rest). General anesthesia was performed under endotracheal intubation through intravenous injection of propofol, fentanyl and vecuronium or rocuronium. In both the elderly (⩾65 years) and middle-aged (<65 years) groups, CAVI and k-CAVI did not change during general anesthesia, whereas baPWV and systolic BP (SBP) showed a statistically significant decrease. Thus, the changes in CAVI (ΔCAVI) and k-CAVI (Δk-CAVI) showed no significant correlations with those of SBP (ΔSBP), whereas the changes in baPWV (ΔbaPWV) were significantly correlated with ΔSBP. ΔCAVI and Δk-CAVI showed no significant differences between the two groups, whereas ΔbaPWV and ΔSBP in the elderly group was much higher than that in the middle-aged group. Measurement of CAVI was not affected by the decrease in BP during general anesthesia. In contrast, baPWV was significantly influenced by changes in BP. These findings suggest that CAVI is a useful index of true arterial stiffness and is superior to baPWV.

Effects of glutamate receptor agonist on extracellular glutamate dynamics during moderate cerebral ischemia

We performed real-time monitoring of the extracellular glutamate dynamics in the rat striatum in vivo using the microdialysis electrode technique, during an experimental penumbral condition of moderate global cerebral ischemia and activated glutamate receptors. The local cerebral blood flow (CBF) was measured with a laser-Doppler probe. One minute after bilateral common carotid artery occlusion (BCAO), CBF was reduced to approximately 60% of the pre-ischemic value and it remained at this level during the period of occlusion. After BCAO, a transient depolarization and a transient increase in extracellular glutamate concentration ([Glu]e) were seen. In other rats, 500 microM N-methyl-D-aspartate (NMDA) was locally micro-transfused for 30 min prior to BCAO. Upon induction of BCAO, an anoxic depolarization-like depolarization and a gradual increase in [Glu]e that continued over the duration of BCAO were seen. After BCAO was terminated, the direct current (DC) rapidly recovered to the basal level, while [Glu]e gradually decreased to the basal level. In rats that were locally micro-transfused with 500 microM Kainate prior to BCAO, DC and [Glu]e did not differ significantly from control. Pretreatment with MK-801 prior to NMDA treatment completely inhibited the NMDA-induced changes in DC and [Glu]e. Pretreatment with NBQX prior to NMDA treatment did not inhibit the NMDA-induced changes in DC and [Glu]e. Consequently, we found that activation of NMDA receptors by elevated [Glu]e exerts an important effect on [Glu]e dynamics in the spreading stroke region very early in the acute stage of cerebral ischemia in vivo.

A questionnaire regarding correspondence to dental patients with psychosomatic disorders

A questionnaire was distributed to dentists who are trustees of the J apanese Society of Psychosomatic Dentistry. All of the respondents are practitioners who treat patients suffering from psychosomatic dental disorders. Approximately 60 percent of them reported the experience of requesting medical insurance fees for psychological testing and psychosomatic medical treatment. About 80 percent hold that dentists are essentially specialists in treating problems of the oral and maxillofacial region and, therefore, take a positive attitude towards the treatment of psychosomatic disorders of this region, also requesting related medical consultations when necessary. The authors also criticize the changes related to psychosomatic medical treatment that came into effect in April, 2006.