Itsuko Ushijima

Effects of preshock experience on enhancement of rat brain noradrenaline turnover induced by psychological stress

The present study examined alterations of brain noradrenaline (NA) turnover as a function of preshock and psychological stress treatments, by measuring contents of NA metabolite, 3-methoxy-4-hydroxyphenylethyleneglycol sulfate (MHPG-SO4), in discrete brain regions of male Wistar rats. Psychological stress induced by exposing to the sight, sound and odor of other rats being shocked produced higher levels of MHPG-SO4 in the hypothalamus, amygdala and locus coeruleus (LC) region, as well as higher levels of plasma corticosterone. Preshock experienced rats also showed marked increases of MHPG-SO4 levels in the same regions described above and elevated plasma corticosterone levels when placed but not shocked in the same environment in which the rats had previously received shocks. The effects of psychological stress on brain NA turnover were affected by the animals shock history preferentially in the hypothalamus and amygdala. These results suggest that: a purely psychological stressor caused acutely enhanced NA turnover in specific brain regions; regional NA activity appeared to be reinstated simply by reexposure to the environment previously associated with shock; preshock experience further intensified the enhancement of amygdaloid NA turnover evoked by psychological stress. An additional experiment, studying the aftereffects of preshock experience, clearly showed that these findings result from sensitization or conditioning to the environment previously paired with shock, and not merely from the aftereffects of the shock per se.

Appearance of Frontal Midline Theta Activity in Patients with Generalized Anxiety Disorder

The appearance of frontal midline theta activity (Fmθ), recognized as distinct EEG theta rhythm in the frontal midline area during performance of a mental task, reflects feelings of relief from anxiety in humans. In the present study, EEGs were recorded, and the Hamilton Rating Scale for Anxiety and the state anxiety scale of Spielberger’s State-Trait Anxiety Inventory were evaluated once a week in 28 patients with generalized anxiety disorder. The Taylor Manifest Anxiety Scale and the trait anxiety scale of Spielberger’s State-Trait Anxiety Inventory were used to assess anxiety before and after the tests. The present results suggest that the appearance of Fmθ might be closely related to an improvement in the anxiety symptoms associated with generalized anxiety disorder.

Differential effects of morphine on core temperature in stressed and non-stressed rats

The effects of morphine on body temperature were studied in rats in two different states - stressed and non-stressed. Morphine injected subcutaneously (s.c.) produced a dual action on body temperature in non-stressed rats. Hyperthermia occurred at lower doses (2.5-10 mg/kg) while hypothermia was produced with a higher dose (20 mg/kg). Both of these effects of morphine were reversed by naloxone (0.1-5.0 mg/kg). Stressing the rats (immobilization with wire mesh) produced slight hypothermia which was markedly potentiated by morphine (5-20 mg/kg) in a dose-dependent manner. Enhancement of hypothermia by morphine in the stressed animals was antagonized by pretreatment with naloxone (0.1-5.0 mg/kg). When rats were treated with morphine (10 mg/kg) 1 h before stress, and were then exposed to immobilization stress, the hyperthermia exhibited in the non-stressed state changed to hypothermia in the stressed state. When the rats which were treated with morphine and then stressed for 1 h were released from stress, the hypothermia observed in the stressed state progressively changed to hyperthermia. Furthermore, these morphine effects, i.e. hyper- and hypothermia in the non-stressed and stressed states, respectively, were reversed but not eliminated by naloxone. These results suggest that the effects of morphine on core temperature in rats are altered depending upon the state of the animals. That is, morphine appears to have a dual action, hyperthermia in the non-stressed state and hypothermia in the stressed state. It also appears that these actions are mediated via opiate receptors.

The Effects of Diazepam on Sleep Spindles: A Qualitative and Quantitative Analysis

The effects of 2.5 or 5 mg diazepam (DIZ) on the sleep spindles were studied in 12 healthy male subjects. Polygraphic recordings and the state anxiety scale of the State Trait Anxiety Inventory (STAI) were made for 6 consecutive nights. An inert placebo was given on the first 3 nights and on the sixth night, and DIZ was administered on the fourth and fifth nights. DIZ produced increases in the amount of the slow and fast spindles in a dose-dependent manner. DIZ dose-dependently lowered the frequency of the fast spindles and elevated that of the slow spindles. Furthermore, the influence of DIZ on fast spindles was greater than that on slow spindles. DIZ decreased the state anxiety of the subjects in a dose-dependent manner. These results suggest that measuring the amount and the frequency of fast spindles could be a useful tool in predicting the anxiolytic effects of benzodiazepines.

A treatment trial with an analog of thyrotropin-releasing hormone (DN-1417) and des-tyrosine-gamma-endorphin in schizophrenia.

Clinical prospects of an analog of thyrotropin-releasing hormone (DN- 14 17) and des-tyrosine-γ -endorphin (DTγ E) in schizophrenia were examined by using the Brief Psychiatric Rating Scale (BPRS) and the electroencephalogram (EEG). Twelve inpatients with chronic schizophrenia were administered fixed doses of neuroleptics throughout the study. Six patients were treated with DN- 1417 (DN-1417 group), and the remaining 6 patients with DTγ E (DYγ E group). One mg/day of DN-1417 or DTγ E was given intramuscularly for 2 consecutive weeks followed by 1 week of no drug treatment. In the DN-1417 group, both total BPRS scores and scores on hallucinatory behaviour and unusual thought content decreased in the first and third weeks. The power values of a and p activities from the frontal area increased in the first and third weeks, whereas an increase in a activity and a decrease of high-fast P activity from the occipital area were obtained during the study. On the other hand, the DTγ E group failed to show either a decrease in BPRS scores or any remarkable EEG changes except for a slight decrease in activity. These results suggest that the positive symptoms of schizophrenia are improved by DN-1417 treatment, and that the alterations in BPRS scores coincide with changes in the frontal EEG.

The relationship between rhythmic activities during a mental task and sleep spindles: A correlative analysis

In a previous study, we suggested that the characteristics of theta, alpha, and beta rhythms during a mental task were similar to those during sleep. Building upon the previous data, correlations between rhythmic activities during a mental task and during sleep were investigated in the present study. Patterns of correlation and no correlation between rhythmic activities during the mental task were similar to those during sleep for subjects with and without frontal midline theta (Fmtheta) activity. In the Fmtheta group, there were no correlations between rhythmic activities in the two situations, while in the non-Fmtheta subjects, theta and alpha rhythms showed a positive correlation with one another, and theta and beta rhythms correlated negatively during sleep. In both groups, there were many correlations between rhythmic activities during the mental task and those in Sleep Stage 2, while there were few correlations between rhythmic activities during the mental task and those in other sleep stages. These results suggest that the mechanism generating rhythmic activities during the appearance of rhythmic activities induced by a mental task may be closely related to those of rhythmic activities during sleep, and that the membrane potentials in reticular thalamic (RE) neurons during the appearance of rhythmic activities induced by a mental task may be nearly equivalent to that in Sleep Stage 2, and that the correlation pattern between the rhythmic activities in each group may be well explained by the appearance pattern of each rhythm in the previous report.

Effects of pertussis toxin on behavioral responses during different withdrawal periods from chronic cocaine treatment

1. The role of Gi-proteins on cataleptic responses induced by SCH23390 and haloperidol in chronic cocaine-treated mice was examined by intracerebroventricullor (i.c. v.) and intravenous (i. v.) injections of pertussis toxin (PTX), which catalyzes adenosine diphosphate (ADP)-ribosylation of Gi-proteins. 2. In animals pretreated chronically with cocaine (10 mg/kg, s.c. on alternating days for 21 days), haloperidol (0.1 mg/kg i.p.) exerted an enhanced cataleptic response, but SCH23390 (0.1 mg/kg i.p.) produced an attenuated response at day 1, which converted to a supernormal response, when it was administered 20 days after the last cocaine injection. 3. The attenuated SCH23390 cataleptic response (D1 receptor supersensitivity induced one day after chronic cocaine treatment), was reversed one day after a single dose of PTX, which by itself had no effect, whereas the enhanced haloperidol catalepsy was further enhanced with same dose of toxin. 4. On the other hand, the enhanced SCH23390- and haloperidol-induced cataleptic responses seen during longer withdrawal period (20 days) were potentiated 20 days after a single coadministration of PTX. The stimulatory effects of PTX on the enhanced SCH23390-induced cataleptic response (D1 receptor subsensitivity induced during long-term withdrawal periods from chronic cocaine treatment), may be due to an indirect inhibition of D1 receptors (a synergistic effect) via blockade of postsynaptic dopamine D2 receptors. 5. The postsynaptic D1 receptor supersensitivity and D2 receptor subsensitivity induced one day after chronic cocaine treatment may involve greater Gi-protein ADP-ribosylation in the presynaptic cell body (VTA) than that in the postsynaptic cell body. On the other hand, the subsensitivity of postsynaptic dopamine D1 and D2 receptors (the enhanced SCH23390- and haloperidol-induced cataleptic responses) seen during longer withdrawal periods may mainly involve Gi-protein ADP ribosylation in the postsynaptic cell body, and which may be mediated by a PTX-sensitive muscarinic M2 and/orGABAB receptor activation.

A qualitative and quantitative analysis of rhythmic activities during a mental task and sleep spindles

The frequency, configuration, and distribution of sleep spindles are similar to some of the rhythmic activities seen during task performance. In the present study, the relationship between rhythmic activities during sleep and arithmetic addition was investigated in male university students with (n = 10) and without (n = 10) frontal midline theta activity (Fmtheta). Electroencephalograms (EEGs) during addition in both groups were compared at frontal and central areas on three consecutive days. Polysomnograms were recorded at the same regions on four consecutive nights for each group. The amount of theta rhythm during a mental task (Fmtheta) and in nocturnal sleep at Fz and Cz electrodes was greater for the Fmtheta group than for the non-Fmtheta group, while the amount of beta rhythm at both sites was smaller in the Fmtheta group than in the non-Fmtheta group. There were no differences between the groups in the amount of alpha rhythm at either site. The frequency of alpha rhythm at Fz and Cz in both situations was slower for the Fmtheta group than for the non-Fmtheta group, but there were no differences in the frequency of theta and beta rhythms between the groups at either site. These results suggest that rhythmic activities during a mental task and in sleep may correlate with each other.