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T Shinba

Publications and source records attributed to T Shinba.

At least 19 recordsLinked to original sources

Clonidine immediately after immobilization stress prevents long-lasting locomotion reduction in the rat.

1. Stress-induced behavioral change in the rat has been utilized as an animal model of anxiety disorder. The authors examined the effect of early intervention by noradrenergic inhibition on stress-induced long-lasting locomotion reduction. 2. Clonidine, an alpha2 agonist, was administered immediately after a single session of 8 min immobilization stress in a restraining box, followed by locomotion measurement on day 1, day 7, and day 14 after the stress session. 3. In the saline-treated control group, locomotion on day 1, day 7, and day 14 after the 8 min stress session was significantly reduced to about 80% in comparison with that before the stress. This finding confirmed the previous report that a single stressful event could lead to long-lasting behavioral changes. When clonidine was administered, locomotion reduction was not observed on any post-stress day. 4. The results suggest that early intervention by noradrenergic inhibition to stressful events may have a preventive effect on subsequent behavioral change which may be considered as an animal model of post-traumatic stress disorder.

Adrenergic alpha-Agonists↗

Spontaneous and auditory-evoked activity of medial agranular cortex as a function of arousal state in the freely moving rat: interaction with locus coeruleus activity.

To characterize the electrophysiological properties of neurons in the medial agranular frontal cortex (Fr2) with respect to arousal level and locus coeruleus (LC) activity, we recorded spontaneous and auditory-evoked single unit activity in these areas simultaneously during different states of arousal in the rat. In the low-arousal state, as determined by EEG, 14/56 Fr2 neurons showed a tonic increase in spontaneous firing rate and 9/56 presented a clear inhibitory response to tone (onset latency 37 ms, duration 200 ms). The inhibitory response was not clear during the high-arousal state. Cross-correlation analysis of pairs of Fr2 and LC units, excluding activity during the actual tone, also showed a negative correlation from 120 ms before, to 170 ms after, Fr2 discharge in 5/63 pairs, only during low arousal. Significantly, 4/5 of the Fr2 neurons having this negative correlation with LC were included in that population which showed a tonic increase in spontaneous firing rate and inhibited to tone during low arousal. LC neurons, on the other hand, all showed excitation to tone stimulation (peak latency 30 ms), and response amplitude was not affected by changes in arousal level. The negative correlation in spontaneous activity, as well as their differential responses to tone, suggests an interaction between a select population of Fr2 neurons and the LC during the low-arousal state. Future studies with lesion or pharmacological manipulations would be necessary to confirm the presence of this interaction.

Animals↗

Random number generation deficit in schizophrenia characterized by oral vs written response modes.

To characterize the deficit in random number generation in schizophrenia with respect to control of sensory information processing, the present study employed a random number generation task using 10 digits (0 to 9) and compared two response modes (oral and written) with different amounts of sensory availability about the previous choices of the subject. Analysis indicated that the increased availability of previous information in the written response mode may exacerbate an aspect of the deficit in random number generation in schizophrenia reflecting the disturbance in control of sensory information processing. The comparison of performance in written and oral response modes may be useful in assessing schizophrenic psychopathology.

Adult↗

Neuronal firing activity in the dorsal hippocampus during the auditory discrimination oddball task in awake rats: relation to event-related potential generation.

In order to investigate the roles of the hippocampus in event-related potential (ERP) generation, extracellular neuronal firings in the dorsal hippocampus were recorded together with the ERPs on the cortical surface and at the hippocampus during the auditory discrimination task in awake rats. The major ERP components on the cortical surface in response to the target tone were the P2, N2, and P3 with the latencies being approximately 100, 200 and 450 ms, respectively. For the non-target tone, the N2 and P3 components were not clearly observed. Local ERP at the hippocampus exhibited similar wave-forms to that on the cortex in response to the target and non-target tones. In the hippocampus, 11 of 21 neuronal firings showed a long-latency sustained activation from 113.6+/-89.7 ms to 539.1+/-208.6 ms with the peak being 281.6+/-167.4 ms after the target tone onset. This increase was not observed after the non-target tone, and was not prominent when the rat did not perform the task. It was not time-locked to lever pressing behavior, and was not affected by the intensity of the tone stimulus. These features in relation to behavioral and paradigm indices were similar to the long-latency ERP components, N2 and P3. Possible involvement of the hippocampus in ERP generation was further suggested by the correlation between the magnitude of the long-latency activation and the amplitudes of N2 and P3 in some hippocampal firings. On the other hand, seven neuronal firings showed a short-latency transient activation with the peak at 36.3+/-14.4 ms accompanied by the early components of local ERP in the hippocampus both after the target and non-target tones. This response was more conspicuous when the rat did not perform the task and its amplitude was positively affected by the stimulus intensity. These findings imply that there are two types of hippocampal neuronal activation during the auditory discrimination oddball task. One is the short-latency activation that is related to information processing of the exogenous stimulus property. The second is the long-latency activation that may be involved in execution of the cognitive task, and in generation of long-latency ERP components.

Animals↗

Phasic increase of monoamine-related electrochemical signal in the rat caudate nucleus following conditioned auditory stimulation during the reaction-time task.

Monoamine-related electrochemical signal was measured by in vivo chronoamperometry at a sampling rate of 5 Hz with a Nafion-coated carbon fiber placed in the caudate nucleus of the rat (n=5) performing an auditory reaction-time task. During the task, the rat pressed a lever in response to a tone stimulus to get food reward. An averaging technique was employed to extract event-related changes in monoamine concentration with respect to the tone stimulus, lever pressing or feeding. It was found that the oxidation current increased phasically for several seconds following the tone presentation with the mean onset latency being 0.4+/-0.2 s. Lever pressing was preceded by the onset of increase in two rats. Prominent increase was not observed following the tone presentation during the resting state, passive feeding, and lever pressing unrelated to the task. The results indicate that phasic increase in monoamine concentration occurs at the caudate nucleus in response to conditioned auditory stimulation in the reaction-time task. This response is not simply the consequence of sensory stimulation, motor reaction, or feeding, but is possibly influenced by integrative processes. The present electrochemical findings are consistent with the previous electrophysiological data on dopamine neuronal activity. However, pharmacological researches will be necessary in order to determine the substance involved in the phasic response.

Acoustic Stimulation↗

[Validation of dissolution testing: evaluation of vibration levels of dissolution apparatuses].

The collaborative study participated by seven laboratories was carried out to develop a dissolution standard for evaluating vibration levels of dissolution apparatuses using enteric-coated granules of cefalexin (EG). Dissolution apparatuses could be divided into two groups according to their vibration levels and the dissolution test results of EG by the rotating basket method at 50 rpm. The critical value of acceleration was about 0.05 m/s2. The upper limit of normal dissolution rates of EG was calculated from the results of the rotating basket method at 50 rpm obtained from low vibration apparatuses. All high vibration apparatuses used in this study were distinguished by the limit from low vibration apparatuses, although most of them were not distinguished by current USP calibrators. These results suggest that EG would be useful as a calibrator for detection of apparatuses on high vibration levels.

Calibration↗

Event-related potentials of the rat during active and passive auditory oddball paradigms.

Event-related potentials (ERPs) of the rat were recorded at the frontal, temporal and parietal areas on the skull during active and passive auditory oddball paradigms, and consisted of P1 (12.7-37.7 ms), N1 (40.0-80.6 ms), P2 (91.7-202.7 ms), N2 (183.7-246.7 ms) and P3 (265.7-462.7 ms) components. Topography and relationship to the paradigm and stimulus types were examined, and unique features were found for each component. P1, N1 and N2 were prominent frontally. However, P2 showed maximum amplitude at the parietal area. N2 and P3 were consistently present only for rare stimuli. During the passive paradigm P3 had a tendency to be greater at the parietal area, but during the active paradigm it had a longer latency and a larger amplitude than during the passive paradigm. No significant difference between the recording sites was observed for P3 latency and amplitude during the active paradigm. The relationship to the paradigm and stimulus types indicates that the rat P3 corresponds to that of the human. There are differences, however, in surface distribution of the ERP components between the rat and the human. The topographical characteristics of the rat ERP, which are possibly due to differences in brain architecture and function, should be taken into consideration when the rat is used for ERP research.

Animals↗

Effects of acute methamphetamine administration on spacing in paired rats: investigation with an automated video-analysis method.

1. Effects of acute methamphetamine administration on spacing and locomotor activity were investigated in paired rats using a computer-assisted automated video-analysis method. 2. Both 0.1 and 1 mg/kg of methamphetamine significantly increased the spacing in comparison with saline. This alteration in behavioral interaction by methamphetamine may serve as one of the animal models of social withdrawal. 3. A significant increase in locomotor activity was found after 1 mg/kg of methamphetamine. 0.1 mg/kg dosage was accompanied by a locomotor change of a lesser degree and shorter duration. 4. The difference with respect to the dose dependency and the time course indicates that the changes in these two behavioral indices by methamphetamine may have different underlying mechanisms.

Animals↗

Event-related potentials in the dorsal hippocampus of rats during an auditory discrimination paradigm.

The relation of the hippocampal neuronal activity to the rat event-related potential (ERP) generation was examined during an auditory discrimination oddball paradigm. ERPs were recorded using a linearly-arranged series of electrodes chronically implanted at the skull, in the frontoparietal cortex, in the CA1 and CA3 regions of the dorsal hippocampus and in the thalamus. The target tone elicited N40, P100, N200, and P450 at the skull electrode. The non-target tone, on the other hand, prominently evoked only the P100 component. At the intracranial electrodes, the ERP amplitude at the latency of the skull P450 was significantly greater in the CA3 region than that at other recording sites, although a phase reversal was not observed. The results indicate that the P450 of the rat may correspond to the human P3, and that the neuronal activity in the hippocampus is involved in its generation.

Adult↗

Increased neuronal firing in the rat auditory cortex associated with preparatory set.

Extracellular single neuronal firings were recorded in the auditory cortex of rats (n = 4) performing a visual reaction-time task with a warning tone (10 kHz, 10 ms duration), which preceded the imperative light stimulus by an interstimulus interval (ISI) of 1.4 s. Thirty-six neuronal firings were evoked by the warning tone, with the peak latency being between 15 and 55 ms. Among them, nine neurons (25%) showed an increased firing frequency following the evoked response during the ISI, which was, in average, 2.5 times as high as the firing frequency during the baseline period. When the tones were presented independent of the imperative stimulus, such sustained increase in neuronal firing was not observed. Activation of the sensory cortex during the ISI may constitute one of the neuronal modulations related to preparatory set.

Acoustic Stimulation↗

Effects of metamfetamine on auditory P3 component of event-related potentials in rats.

Three rats were trained with an oddball paradigm, in which 5 kHz frequent and 10 kHz target rare tones were presented with a probability of 0.8 and 0.2. Pressing the lever within 2 s following the onset of the target tones was rewarded with a drop of food paste. Long latency event-related potentials (ERPs) corresponding to those in humans could be recorded in rats. After the administration of metamfetamine (0.2 mg/kg), the amplitude of surface and intracortical N1 increased, indicating an augmentation of the primary cortical response. Surface P3 showed a decrease of amplitude, accompanied by an increase of intracortical negativity. These alterations of ERPs may be caused by the dysregulation of central noradrenergic system.

Amphetamines↗

Event-related potentials during an auditory discrimination task in rats.

Event-related potentials (ERPs) during an auditory discrimination task were recorded both on the surface and at a depth of the auditory cortex in rats. Ten-kilohertz rare and 5-kHz frequent tones were used with the probabilities of 0.2 and 0.8. Lever pressing within 2 s, following the onset of the rare tone, was rewarded with food paste. In the performing condition, the surface ERPs for the rare tones consisted of P30, N50, P80, N130, and P290 components. Only the surface P30 and N50 showed a polarity reversal at the intracortical electrode, suggesting that these components are generated in the auditory cortex. The P290 was elicited in the performing condition but not in the resting condition, showing its task-relevancy. These results suggest that auditory ERPs similar to those in humans can be recorded in rats during an active discrimination task.

Acoustic Stimulation↗

Possible noradrenergic dysfunction in schizophrenia.

In spite of extensive studies over the last 2 decades to find direct evidence in support of the dopamine hypothesis of schizophrenia, no undisputed experimental data has been obtained. In contrast, estimation of noradrenalin (another major catecholamine) and its metabolites in postmortem brain and in the cerebrospinal fluid appears to be producing consistent results. To understand the meaning of this change for the pathogenesis of the illness, we have carried out animal experiments in which reproducibility of schizophrenic signs and symptoms by noradrenergic dysfunction, and treatability of the disorder by modulation of noradrenergic activity were studied. First, psychophysiological signs in skin conductance responsiveness (nonhabituating or nonresponding change) and smooth pursuit eye movement (spiky or stepwise pursuit) could be reproduced by enhancing or suppressing central noradrenergic activity. Behavioral abnormalities resembling schizophrenic symptoms are known to be reproducible by over- or underactivity of the system (overarousal or underarousal syndrome). Secondly, the action of various drugs capable of modulating schizophrenic symptoms was analyzed in relation to noradrenergic activity. Haloperidol, in particular, had a potent suppressing effect on skin conductance activity (spontaneous fluctuation rate and habituation rate) when administered chronically, suggesting its inhibitory action on noradrenergic activity.

Animals↗

Functional influence of the central noradrenergic system on the skin conductance activity in rats.

Pharmacological studies on neuroleptics and amphetamine strongly suggest that some dysfunction of the central catecholamine system may play a key role in the pathogenesis of schizophrenia. Our previous studies have demonstrated that intraventricular administration of 6-hydroxydopamine, a selective neurotoxin of the catecholamine neuron, can reproduce schizophrenia-like abnormalities in the skin conductance activity. In the present experiments, effects of pharmacological modulation of the central noradrenergic activity were studied in rats. Stimulation of the central noradrenergic activity by yohimbine (0.6 mg/kg, i.m.) slowed down the habituation of the skin conductance response (SCR) and increase the spontaneous fluctuation of the skin conductance (SF), while inhibition of the activity by clonidine (0.06 mg/kg, i.m.) accelerated or obliterated the SCR and decreased the SF frequency. If the functional significance of the central noradrenergic system lies in vigilance control, the present results are consistent with classical theory in psychophysiology: the habituation rate of SCR and the frequency of SF are correlated well with each other and both indices reflect arousal level. The disorder of the system should produce not only these psychophysiological abnormalities but also psychological disturbances; i.e., overarousal and underarousal syndromes. Therefore, the dysfunction of the noradrenergic system might constitute an essential aspect of schizophrenic disorder.

Acoustic Stimulation↗

Alcohol consumption and insomnia in a sample of Japanese alcoholics.

The amount of ethanol consumed by chronic alcoholics in a Japanese slum area with persistent insomnia (n = 40) and those without it (n = 40) was compared using a questionnaire. For both groups, the present habitual consumption (PHC) of ethanol per day was most frequently between 60 g and 150 g and no difference was observed between the two groups. In contrast, the maximum habitual consumption (MHC) of ethanol per day throughout the alcoholic history was found to be greater for the insomnia patients than the non-insomniacs (p < 0.001). No difference between the groups was found in the kind of alcoholic drink consumed, with sake (Japanese rice wine) being the most popular in both groups. The results suggest that persistent insomnia in alcoholics is related to excessive alcohol intake and persists even when drinking levels have fallen.

Adult↗

Auditory-evoked response of the cortex after yohimbine administration: phase advance effect of central noradrenergic activation.

The effects of central noradrenergic activation on an auditory-evoked cortical response were studied using systemic administration of yohimbine (2 mg/kg intravenously, IV), a noradrenergic stimulant, in 13 anesthetized rats. To analyze changes of the response, surface and intracortical evoked potentials (EP) as well as extracellular single-unit recordings with tungsten microelectrodes were employed. It was noted that the initial-positive wave of the surface EP corresponded to unit firing responses in a restricted area of the auditory cortex, where the surface EP was largest and a polarity inversion of the intracortical EP was observed. The following effects were produced by yohimbine: 1) The initial-positive surface potential (n = 10) and corresponding intracortical potential with inverted polarity (n = 6) both showed an increase in amplitude and a decrease in peak latency; 2) the unit firing response (n = 10) tended to show an increase in peak frequency and a decrease in peak firing latency; and 3) yohimbine produced an earlier ending of the firing period, and in paired stimulation experiments (n = 7) it prolonged the period during which the second response was suppressed, indicating an augmentation of postexcitation inhibition. Later histological examination suggested that most of the units recorded were pyramidal cells. These findings indicate that chemical stimulation of the central noradrenergic system by yohimbine enhances both the initial excitatory and following inhibitory processes in the auditory-evoked response of the cortical units (probably pyramidal cells), resulting not only in amplification of the response but also in advancement of the response phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

The characteristics of the antidromic discharge of cat dorsal raphe neurons during repetitive activation.

Slowly discharging neurons in the cat dorsal raphe could be classified into 3 types according to the behavior of antidromic spike discharges during repetitive stimulation of the medial forebrain bundle at 10 Hz. In the types 1 and 2, the latency of antidromic discharge was gradually prolonged to reach an asymptote, whereas no marked change occurred in the type 3. The type 2 neurons, which had a slower conduction velocity, showed a greater prolongation than the type 1 neurons. The maximum length of this prolongation was not significantly correlated with the initial latency. During 10 Hz stimulation some neurons showed repeatedly a conduction block after a sequence of initial decrease and later increase in latency. The spontaneous discharge was strongly suppressed during 10 Hz stimulation. During 1 Hz stimulation just after the cessation of 10 Hz stimulation, the prolonged antidromic latency was gradually restored in parallel with the recovery of the spontaneous discharge. Circumstantial evidences seem to be in favor of the idea that hyperpolarization of the axonal and somatic membranes is mainly responsible for the observed behavior of antidromic spikes of type 1 and 2 neurons.

Animals↗

Two types of rostroventral medulla neurons projecting to the trigeminal spinal nucleus as differentiated by the response to antidromic activation and the histological location.

A population of neurons in the rostroventral medulla, which send their axons to the subnucleus oralis of the trigeminal spinal nucleus of rats, could be differentiated into two types on the basis of their location and the variability of antidromic latency during repetitive stimulation at 10 Hz. Type A neurons were mostly located in the raphe magnus and were activated antidromically with a relatively long latency, which gradually increased during repetitive stimulation. By contrast, type B neurons were located in the medial portion of the gigantocellular reticular nucleus, and responded with a relatively short, stable antidromic latency.

Animals↗