Harumi Matsuda

The modified light/dark transition test in mice: Evaluation of classic and putative anxiolytic and anxiogenic drugs

1. We devised a new light/dark transition apparatus, recorded transitions, % time animals spent outside the dark chambers (% time) and locomotor activity, and evaluated this apparatus by testing anxiolytics, non-anxiolytic drugs and putative anxiogenic drugs in mice. 2. Diazepam and alprazolam significantly increased transitions, % time and locomotor activity. The effects of 1 mg/kg (i.p.) diazepam on these parameters in this modified test were blocked by flumazenil, a selective benzodiazepine antagonist. 3. Anxiogenic drugs such as beta-carboline-3-carboxylic acid ethyl ester (beta-CCE) and picrotoxin significantly decreased all three parameters. Another anxiogenic drug, yohimbine, also significantly decreased transitions and locomotor activity, but it significantly increased % time at 5 mg/kg (i.p.). 4. Imipramine (5-10 mg/kg, i.p.), an antidepressant, sulpiride (10-25 mg/kg, i.p.), an antipsychotic drug, and scopolamine (0.1-1 mg/kg, i.p.), an anticholinergic drug, had no effect. 5. Buspirone, a partial 5-HT1A receptor agonist, produced parameter changes similar to those induced by anxiolytic benzodiazepines. 8-OH-DPAT, a full 5-HT1A receptor agonist, significantly increased transitions and locomotor activity but not % time. 5-HT3 receptor antagonists, ICS205-930 and MDL72222, did not have any effect on these parameters. 6. Methamphetamine (1-2 mg/kg, i.p.) increased all parameters, while caffeine increased only locomotor activity. 7. The present findings indicate that the modified light/dark transition test is very simple and easy to perform for testing the anxiolytic and anxiogenic effects of drugs.

Effects of water ingestion on gastric electrical activity and heart-rate variability in healthy human subjects

Electrogastrography (EGG) is a method to record electrical activity of the stomach using cutaneous electrodes. Power ratio (PR) is one of the parameters and means the relative change of EGG power of gastric activity from before to after certain stimulations (e.g., meals, water or drugs). Autonomic nervous function is an important modulator of gastric activity, but its relation with the EGG parameters has not been well clarified. We recorded EGG and the R-R interval simultaneously both before and after drinking 150 ml water for 400 s, and spectrally analyzed them using the maximum entropy method in 12 healthy volunteers. We calculated PR from before to after water ingestion, and the power of the high-frequency component of R-R interval variability before (pre-HF) and after water ingestion (post-HF), and their ratio (rHF = post-HF/pre-HF). PR was positively correlated with rHR (r = 0.727; P < 0.05) and negatively correlated with pre-HF (r = 0.706; P < 0.05), and rHF was negatively correlated with pre-HF (r = 0.776; P < 0.05). These results suggest that simultaneous recording of EGG and ECG for frequency domain analysis is necessary to estimate the vagal nervous activity.

The responses of skin blood flow, mean arterial pressure and R-R interval induced by cold stimulation with cold wind and ice water

This study was designed to evaluate the peripheral circulation response to cold wind stimulation. Skin blood flow (SBF), ECG R-R intervals (RRs) and mean arterial pressure (MAP) were measured in ten healthy men under strictly controlled conditions. Cold wind flow and ice water bath were prepared as cold stimulations. The subjects were exposed to each cold stimulation and the values of the responses were simultaneously recorded. The cold wind stimulation reduced SBF (maximally 40.4 +/- 3.2%) and increased MAP (maximally 106.9 +/- 1.3%), but did not affect RRs. On the other hand, all parameters were affected by the ice water stimulation, which reduced SBF to 16.4 +/- 1.2% and RRs to 85.1 +/- 3.0%, and increased MAP to 130.6 +/- 2.4% compared with the control state. All subjects suffered from intense pain during the ice water but not the cold wind stimulation, and two of them were eliminated from this study because of vagotonia. After phentolamine iontophoresis was used to block the receptor of peripheral alpha-adrenergic nerve terminals, the cold wind stimulation did not affect SBF. These results suggest that cold wind stimulation is a useful test for evaluating peripheral alpha-adrenergic nerve function in relation to cold sensation, without increase of RRs and noxious pain.

Relationship of the ipsilateral rotation in night period and striatal dopamine content reduction in unilateral nigrostriatal 6-OHDA lesioned rats

In order to discriminate well-lesioned rats after unilateral microinjection of 6-OHDA into the nigrostriatal dopamine system, we measured the spontaneous rotation in the night period and calculated the rate of ipsilateral rotation movement. The rate of ipsilateral rotation movement increased along with the total rotation movement. The rats with over 95% of ipsilateral rotation kept the rate relatively constant for 4 weeks after 6-OHDA lesion and showed a significant increase of contralateral rotation (253.2 +/- 37.9) as compared with the rat that had lower than 95% ipsilateral rotation (3.6 +/- 1.4) after the injection of apomorphine (0.25 mg/kg, s.c.). The reduction percentages of striatal DA contents in animals with unilateral rotation over 95% and under 95% to the lesioned side were 97.8 +/- 0.6% and 59.6 +/- 5.8% (P < 0.001), respectively. The rats with over 90% reduction of striatal DA levels corresponded nicely to rats with 95% ipsilateral rotation among rats injected with apomorphine. These results suggested that the evaluation of ipsilateral rotation, taken the level of 95% rotation to the lesioned side as a standard, was able to discriminate well-lesioned rats without apomorphine treatment after unilateral nigrostriatal 6-OHDA application.

Cases Study of Saiko-sokan-to

柴胡疎肝湯は, これまで心労, 不眠, 術後腸管癒着, 四逆散証で左脇痛, 四逆散証で肝気胸協の鬱塞などの症状に対し奏効した報告がなされているが, 投与目標は不明の点も多い。今回, 肩こり, 頭痛, 腹部膨満感, のぼせ感等の症状に対し柴胡疎肝湯が奏効した7症例を経験した。これら7症例の検討より柴胡疎肝湯の投与目標として (1) 胸脇苦満, (2) 心下痞鞭, (3) 気鬱が考えられた。また重度の〓血証では『一貫堂』の柴胡疎肝湯が有効であった。