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.

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.

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.

Modification of cataleptic responses to dopamine receptor antagonists after withdrawal from chronic cocaine or cocaine plus dopamine antagonist administration.

1. In mice pretreated chronically with cocaine (indirect dopamine agonist: 10 mg/kg, s.c. on alternating days for 15 days), haloperidol (dopamine D2 antagonist: 0.3 mg/kg i.p.) exerted an enhanced cataleptic response, but SCH23390 (dopamine D1 antagonist: 0.3 mg/kg i.p.) produced an attenuated response at 24 h, which converted to a supernormal response, when it was administered 15-60 days after withdrawal from cocaine. 2. A challenge dose of SCH23390 exhibited enhanced catalepsy when given 15 days, but not at 24 h, after the last pretreatment dose of SCH23390 (0.1-1.0 mg/kg s.c.). In contrast, haloperidol catalepsy was not affected by the SCH23390 pretreatment. 3. However, in animals chronically pretreated with haloperidol (0.1-1.0 mg/kg s.c.), a challenge dose of SCH23390 as well as haloperidol exhibited attenuated cataleptic effects at 24 h and normal cataleptic responses at 15 days after the last dose of the pretreatment regimen. 4. Challenge doses of haloperidol or SCH23390 given to mice 24 h after chronic cocaine pretreatment produced enhanced and attenuated cataleptic responses, respectively; however, these responses were no longer produced when haloperidol or SCH23390 was given to mice pretreated chronically with a combination of cocaine and either haloperidol or SCH23390. 5. The enhanced catalepsy produced by a challenge dose of SCH23390 (15-60 days after chronic cocaine) was further potentiated when it was administered to animals that had been pretreated chronically with a combination of SCH23390 and cocaine, but was antagonized in animals pretreated chronically with haloperidol and cocaine. In contrast, the degree of enhanced cataleptic responses produced by a challenge dose of haloperidol 30-60 days after pretreatment chronically with a combination of cocaine + SCH23390 was similar to that seen after chronic cocaine alone. However, this enhanced response was antagonized in animals that had been pretreated chronically with the combination of cocaine + haloperidol. 6. The results suggest that the coadministration of SCH23390 with cocaine was able to block indirectly dopamine D2 receptor inhibition (subsensitivity) induced during the early withdrawal period from chronic cocaine, despite the fact that by itself SCH23390 did not have an effect on haloperidol catalepsy. Accordingly, the stimulatory effects of dopamine D2 receptors by a single administration of cocaine may be mediated mainly by an indirect stimulation of dopamine D2 receptor function via its D1 receptor stimulating action. 7. The coadministration of SCH23390 with cocaine rather aggravate the subsensitive effect of dopamine D1 receptors (increased SCH23390 catalepsy) produced during long-term withdrawal period from chronic cocaine, but did not affect that of the dopamine D2 receptor. On the other hand, the coadministration of haloperidol with cocaine normalized both D1 and D2 receptor subsensitive effect. 8. These result suggest that a single administration of SCH23390 or haloperidol after long-term withdrawal periods from chronic cocaine may not be effective as antipsychotic drugs because of further aggravation of suppressive behaviors. These results also provide evidence that D2 receptor antagonists may be more effective as antipsychotic drugs than dopamine D1 receptor antagonist, since the coadministration of haloperidol with cocaine normalized the abnormal behaviors seen during early and long-term withdrawal periods from chronic cocaine.

Cocaine: evidence for NMDA-, beta-carboline- and dopaminergic-mediated seizures in mice.

The present study was undertaken to examine the role of the benzodiazepine/GABA and N-methyl-d-aspartate (NMDA) systems in the convulsive effect of cocaine in mice. When cocaine (3.5 mg/ml) solution was infused into the tail vein at a rate of 0.3 ml/min, mice showed clonic and tonic convulsions. These seizures were not affected by low doses of bicuculline or picrotoxin, a GABAA receptor antagonist and a Cl ion channel blocker, respectively. Aminooxyacetic acid (AOAA), a GABA deaminase inhibitor, and phenobarbital, a Cl ion channel activator, and baclofen, a GABAB receptor agonist, also had no effect on these convulsions. Benzodiazepine inverse agonist beta-DMCM, at a dose which by itself had no convulsive effect lowered the convulsive threshold of cocaine. This lowered convulsive threshold was reversed by flumazenil, a benzodiazepine inverse antagonist, and diazepam, a benzodiazepine full agonist, which by themselves did not inhibit cocaine seizure. It is likely that cocaine seizure involves a benzodiazepine (beta-carboline) recognition site other than the benzodiazepine/GABAA receptor-Cl ionophore complex system. CPP and MK-801, competitive and noncompetitive NMDA receptor antagonists, respectively, inhibited cocaine seizures. The inhibitory effects of CPP on cocaine convulsion were reversed by a low dose of NMDA, which by itself did not induce seizure. A dopamine D1 receptor agonist SKF38393 enhanced both clonic and tonic convulsions, while a dopamine D2 receptor agonist bromocriptine inhibited these convulsions. These stimulatory and inhibitory effects were reversed by the D1 and D2 receptor antagonists, SCH23390 and haloperidol, respectively. These results suggest that the cocaine-induced convulsion may involve an activation of the NMDA-Ca ionophore complex system, which is mediated by the dopaminergic system, and a beta-carboline recognition site other than the benzodiazepine/GABAA receptor-Cl ionophore complex system.

Anxiolytic effects of low-dose clomipramine in highly anxious healthy volunteers assessed by frontal midline theta activity.

1. The appearance of Fm theta, the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, reflects relief from anxiety in humans. 2. In the present study, the anxiolytic effects of low-dose clomipramine were examined by monitoring the Fm theta amount, the STAI scores and the plasma 5-HIAA concentration in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. 3. Subjects were given placebo, 10 mg and 30 mg clomipramine in a double-blind crossover design. Blood samples were obtained, STAI scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 3 hrs after drug administration. 4. In the non-Fm theta group, 10 mg clomipramine decreased the 5-HIAA concentration and state anxiety scores but increased the Fm theta amount, while 30 mg clomipramine slightly increased only the Fm theta amount. However, there were no differences in these items before and after clomipramine administration in the Fm theta group. 5. These results suggest that low doses of clomipramine such as 10 mg may exert anxiolytic effects during the acute phase of treatment in highly anxious humans.

Stress-dependent antinociceptive effects of carbamazepine: a study in stressed and nonstressed rats.

1. The present study examined the antinociceptive effects of carbamazepine on the tail flick test in stressed and nonstressed rats. 2. Carbamazepine produced a bimodal antinociceptive effect in stressed rats, the first peak appearing 30 min and the second 4 h after injection. Antinociceptive effect was not observed in nonstressed rats. 3. The secondary, but not the initial, carbamazepine antinociception in stressed rats was blocked by naloxone (0.2 mg/kg, i.p.), an opioid receptor antagonist. 4. Caffeine (5 mg/kg, i.p.), an adenosine A1/A2 receptor antagonist, inhibited the both initial and secondary antinociceptive effects of carbamazepine in stressed rats. 5. Carbamazepine increased the antinociceptive effect induced by either i.p. or i.c.v. administration of N6-cyclohexyl adenosine (CHA), an adenosine A1 receptor agonist, in stressed rats, but decreased it in nonstressed rats. 6. These results suggest that the initial antinociceptive effect of carbamazepine in stressed rats may be produced via an activation of the adenosine A1 receptors, such as was produced by CHA. The secondary long-lasting antinociceptive effects of carbamazepine may be mediated by an activation of opioid systems. 7. Furthermore, the initial activation of the adenosine A1 receptors by carbamazepine may be a triggering factor for the subsequent long-lasting activation of the opioid system, which results in the antinociception effects.

Dopaminergic and cholinergic interaction in cataleptic responses in mice.

The cataleptogenic effects of haloperidol, a dopamine D2 receptor antagonist; SCH23390, a D1 receptor antagonist; physostigmine, a cholinesterase inhibitor; and pilocarpine, a muscarinic M1 receptor agonist, were challenged by pretreatment of mice with SKF38393, a dopamine D1 receptor agonist; apomorphine, a dopamine D1/D2 receptor agonist (mainly D2 receptor); pirenzepine, a muscarinic M1 receptor antagonist; and scopolamine, a muscarinic M1/M2 receptor antagonist. The effect of physostigmine and pilocarpine on haloperidol and SCH23390 cataleptic responses was also examined. Each of the challenging agents blocked one or more of the cataleptogenic agents, but only scopolamine blocked all four. Pirenzepine blocked cataleptic responses induced by SCH23390 and pilocarpine, but not those by haloperidol and physostigmine. The results of this study suggest that the action of physostigmine (endogenous acetylcholine) on M2 receptors might be more potent than that on muscarinic M1 receptors. A further interesting observation was that the haloperidol-induced catalepsy was enhanced by physostigmine pretreatment, but not by pilocarpine pretreatment, whereas the SCH23390-induced catalepsy showed the opposite spectrum of enhancement by the two cholinergic agonists. We conclude that, although the four cataleptogenic agents act via the dopaminergic-cholinergic systems, their pharmacological differences may be due largely to the different receptor subtypes that are involved in the mediation of catalepsy produced by each agent. Thus, dopamine receptors not only influence the cholinergic muscarinic receptors, but muscarinic M1 and M2 receptors also might mediate dopamine D1 and D2 receptor responses, respectively. The results suggest that there are, at the least, relationships between muscarinic M1 receptors and dopaminergic D1 receptors, and between muscarinic M2 receptors and dopaminergic D2 receptors. Dopamine D1 and D2 receptors may interact in a synergistic fashion on dopaminergic systems, but act independently of each other in influencing other system such as cholinergic neurons.

Differential effects of dopaminergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety.

1. The appearance of frontal midline theta activity (Fm theta), the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, indicates relief from anxiety in humans. 2. The authors examined the effects of bromocriptine and sulpiride on anxiety and arousal in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. Subjects were given placebo, 2.5 mg bromocriptine and 100 mg sulpiride in a double-blind crossover design. 3. Blood samples were obtained, STAI scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 1 hr after drug administration. 4. Bromocriptine reduced the HVA concentration in both groups; sulpiride caused an increase in both groups. In the Fm theta group, bromocriptine did not alter the appearance time of Fm theta, the state anxiety score or the task performance; sulpiride increased the Fm theta amount and reduced the state anxiety but did not affect the task performance. In the non-Fm theta group, bromocriptine increased the Fm theta duration and reduced the state anxiety score but did not influence the task performance, while sulpiride reduced Fm theta and increased the state anxiety but had no effect on the task performance. 5. These results suggest that the sensitivity of presynaptic D2 receptors is higher in high-anxiety subjects compared with low-anxiety subjects, and that anxiolytic effects in high-anxiety humans and those in low-anxiety humans may be caused by decreased and increased DA activity, respectively. In addition, the stimulation of DA function may cause anxiogenic effects in high-anxiety individuals.

Effects of dopamine antagonists on changes in spontaneous EEG and locomotor activity in ketamine-treated rats.

We investigated the effects of dopamine antagonists on spontaneous cortical and hippocampal electroencephalographic (EEG) changes, and on hyperlocomotion in ketamine-treated rats. Ketamine (20-60 mg/kg IP) synchronized cortical EEG and desynchronized hippocampal EEG in a dose-dependent manner indicating that the drug induced a dissociation between the cortical and hippocampal EEG. These EEG changes were accompanied by an increase in spontaneous locomotor activity, which involved lack of focused direction, stereotypy, irritability and other abnormalities. Dopamine antagonists, such as haloperidol (0.3-1 mg/kg IP), and nemonapride (0.3-1 mg/kg IP), reversed the dissociation between the cortical and hippocampal EEG in ketamine (60 mg/kg IP)-treated rats. Ketamine-induced hyperlocomotion was also decreased by administration of haloperidol (0.3 and 1 mg/kg IP) or nemonapride (0.1-1 mg/kg IP). Thus, it was found that dopamine antagonists reversed the EEG alterations and behavioural changes in ketamine-treated rats.

Differential effects of noradrenergic drugs on anxiety and arousal in healthy volunteers with high and low anxiety.

1. The appearance of frontal midline theta activity (Fm theta), the distinct EEG theta rhythm in the frontal midline area during performance of a mental task, indicates relief from anxiety in humans. 2. The authors investigated the effects of clonidine and yohimbine on anxiety and arousal in 24 male university students with (Fm theta group, n = 12) and without (non-Fm theta group, n = 12) Fm theta. Subjects received placebo, 0.15 mg clonidine and 15 mg yohimbine in a double-blind crossover design. 3. Blood samples were obtained, state-trait anxiety inventory (STAI) scores were determined, and EEGs were recorded before and during the performance of an arithmetic addition task. The test was repeated twice: before and 1 hr after drug administration. 4. Clonidine reduced the 3-methoxy-4-hydroxyphenylglycol (MHPG) concentration in both groups; yohimbine caused an increase in both groups. In the Fm theta group, clonidine reduced the appearance time of Fm theta and the number of task performance but did not alter the state anxiety scores; yohimbine had no effects on Fm theta or the state anxiety but increased the task performance. In the non-Fm theta group, clonidine increased the Fm theta amount and reduced the state anxiety score but did not affect task performance, while yohimbine reduced Fm theta but increased the state anxiety, the task performance and the number of errors. 5. These results suggest that changes in noradrenaline (NA) activity affect both anxiety and arousal levels in high-anxiety humans, but predominantly affect only the arousal level in low-anxiety humans.

An automatic sleep-stage analysis system with off-line high-speed processing using a super mini-computer.

An automatic sleep analysis system using a super mini-computer was developed. The system improved and expanded the data processed by the mini-computer. It had the following features: 1) wave-forms were collected and analyzed at a high speed (reproduced at 10 or 20 times the speed of a data recorder) by an off-line procedure to utilize the computer resources more efficiently; 2) all information and the original wave-forms were output to a laser printer because of the lower cost and more efficient arrangement of the data; 3) various wave-form parameters were measured by wave-form analysis; 4) the application program was based on general-purpose language; and 5) wave-form reanalysis and reconstruction of the logic was easily implemented for automatic evaluation of the sleep stages. Automatic analysis of the sleep stages was impossible for 15 of 1484 periods (20 sec per period) with one of the cases analyzed, and 142 of 1484 periods had to be corrected because of erroneous identification.

Automatic analysis of sleep spindles--assessment in one case treated with a benzodiazepine anxiolytic drug.

Wave-form analysis and detection of sleep spindles should be automatically performed to achieve objective and highly precise determination of the pattern of appearance of sleep spindles. The conditions for constructing the automatic analysis and detection are as follows: 1) it is recommended that EEGs be sampled at 500 Hz or higher intervals; 2) the digital filter with the threshold that is most appropriate for removal of artifacts should be used; 3) various conditions for the analysis and detection of wave-forms are widely used; and 4) a procedure for inspecting and reading record paper should also be included in the set-up. Taking these points into consideration, the authors developed an automatic analysis system for sleep spindles, which employs a computer. The system was applied to a case preliminarily treated with a benzodiazepine anxiolytic drug, ethyl loflazepate (CM6912). The assessment using this system revealed that the CM6912 administration induced an increase in sleep spindles, delayed frequency, and caused amplitude increases and a prolonged duration.

Analysis of sleep EEGs by the interval histogram method--validity of the baseline night as a control and the effect of ethyl loflazepate (CM6912).

The effects of an anxiolytic drug, ethyl loflazepate (CM6912) on sleep EEGs were investigated by the interval histogram method originally developed. EEGs were classified into each of the delta 2-beta 2 and sigma 1 wave-form parameters, and the individual frequencies were determined on the third baseline, second drug and the first recovery nights in each sleep stage. In comparison with the second baseline night, the sigma 1 waves in stage 2 sleep and the delta 1 waves in REM sleep were decreased and the alpha and sigma 1 waves in stage 3 sleep were increased on the third baseline night. In consideration of the 5% significance level and the remarkable influence of drug administration, described below, no major problems were encountered in the use of the night as a control in this experimental schedule. The main characteristics of administration of CM6912 manifested as decreases in the slow wave, increases in the fast wave, and an increase in the sigma 1 wave in sleep stages other than stage 1. These tendencies were remarkable on the second drug night and were still evident even on the recovery night. Increases in sigma 1 wave were related to increases in sleep spindles. The increases in the beta 2 wave were particularly remarkable in REM sleep.

Stimulatory effect of butoctamide hydrogen succinate on REM sleep in normal humans.

1. The efficacy of butoctamide hydrogen succinate (BAHS) was compared with that of nitrazepam on the basis of the polysomnograms and the subjective assessments. 2. Twelve healthy male students were divided into three groups consisting of 4 subjects each with were administered BAHS 600 mg, nitrazepam 5 mg, and BAHS 600 mg + nitrazepam 5 mg, respectively. 3. Polygraphic recordings were made for 8 consecutive nights for each subject, and the polysomnograms were evaluated by computerized automatic analysis using the interval histogram method. 4. An inert placebo was administered on the first 3 nights and on the seventh and eighth nights, and the test article regimen was administered on the fourth, fifth and sixth nights. 5. The test articles and the placebo were administered orally at 22:30 hr, and the recording of polysomnograms was started at 23:00 hr and ended at 8:00 hr the next morning. 6. The subjects were requested to fill out the subjective assessment of sleep before falling asleep and after arising the next morning. 7. BAHS increased REM sleep and decreased stage 2 sleep significantly; however, it failed to affect stage 1, 3 or 4 sleep. 8. Nitrazepam increased significantly the total sleep time and stage 2 sleep but decreased significantly the stage 3 sleep and decreased slightly the stages 1, 4 and REM sleep. 9. The combined treatment with BAHS and nitrazepam did not alter the sleep parameters except for increasing the total sleep time. 10. No obvious changes were observed in the subjective assessments after administration of the drugs. 11. These findings suggest that BAHS results in a unique sleep pattern different from benzodiazepines, and that BAHS may be suitable for treating insomnia in elderly patients and those with drug abuse, manic-depressive illness or schizophrenia.

Characteristics of the anxiolytic effects of buspirone in high- and low-anxious normal humans assessed by frontal midline theta activity.

Fmtheta is a distinct theta activity in the frontal midline area that appears during performance of mental tasks. It is suggested that relief from anxiety might be reflected in the appearance of Fmtheta. In the present study, the anxiolytic effects of buspirone were investigated using 24 male university students with (Fmtheta group, n = 12) and without (non-Fmtheta group, n = 12) Fmtheta. The subjects were given placebo, buspirone 5 mg and 15 mg in a double-blind, crossover design. Blood samples were obtained, scores were made on the State Trait Anxiety Inventory (STAI), and EEGs were recorded before and during performance of an arithmetic addition. The test was repeated twice: before and 1 h after drug administration. In the Fmtheta group, buspirone dose-dependently produced a decrease in plasma 5-HT and 5-HIAA concentrations and in state anxiety scores and an increase in Fmtheta amounts. In the non-Fmtheta group, however, there were no differences in these items except for 5-HT concentration before and after buspirone administration. These results suggest that anxiety in the Fmtheta group is mainly correlated with 5-HT1A receptor function, and that buspirone may have anxiolytic effects in patients with reactive anxiety but not those with endogenous anxiety.

Memory and cognitive impairments in a case of long-term trihexyphenidyl abuse.

We present a case of long-term trihexyphenidyl (THP) abuse in which memory and cognitive impairments were observed 23 years after the commencement of medication. This case showed a dramatic improvement after withdrawal of THP. Clinical course during admission was followed with psychometric testing and laboratory examinations. The fact that the patient showed no evidence of lowered alertness during the clinical course raises the possibility that THP can primarily induce impairment of memory and cognitive functions. This is supported by the findings on the resting EEG of the patient. This case emphasizes the need to exercise caution in prescribing high doses of anticholinergic agents for long periods, particularly in elderly patients with underlying brain pathology.

Effects of mianserin in chronic schizophrenia.

1. The efficacy of mianserin as a supplement in treating chronic schizophrenia was tested by monitoring the BPRS and plasma monoamine metabolites. 2. Twenty inpatients with schizophrenia were administered fixed doses of neuroleptics throughout the study. 3. A control BPRS scoring and blood sampling were done before mianserin administration. 4. Fixed doses of 60 mg/day of mianserin for 2 weeks and flexible doses for 4 weeks were given orally in an open study for 6 consecutive weeks, and no treatment followed for 1 additional week. 5. BPRS scoring was carried out once weekly, and blood samples were obtained after mianserin treatment. 6. Both total BPRS scores and scores for negative symptoms were decreased by mianserin treatment as compared with the control values. 7. 5-HIAA concentrations of both responding patients and nonresponding patients to mianserin were increased after medication; however, 5-HIAA values of responding patients were lower than those of nonresponding patients. 8. HVA concentrations of the responding group were slightly increased by mianserin administration. 9. There were no significant changes in MHPG levels between the two groups. 10. These results suggest that the negative symptoms of schizophrenia are partly improved by mianserin treatment.

Differential responses to mental stress in high and low anxious normal humans assessed by frontal midline theta activity.

The distinct EEG theta rhythm from the frontal midline area observed during performance of mental tasks has been called Fm theta. In the present study, plasma catecholamine responses to mental stress were investigated using male students with (n = 12) and without (n = 12) Fm theta. The subjects were requested to complete the trait anxiety scale of STAI, and control blood samples were obtained. 65 min later, their EEGs were recorded during performance of an arithmetic addition task for 5 min. The state anxiety scores of STAI were obtained twice before and after the EEG recording. Blood samples were drawn three times during the state anxiety test and the EEG recording. The Fm theta appearance group showed low trait anxiety and a decrease of state anxiety after the mental task; however, the Fm theta non-appearance group exhibited high trait anxiety and no changes of state anxiety before and after the mental task. The concentrations of DA, HVA, NA and MHPG in the Fm theta appearance group showed lower levels at all times compared to those in the non-appearance group. In the Fm theta appearance group, an increase of DA turnover was observed by the addition of mental task. On the other hand, the Fm theta non-appearance group showed an increase of NA turnover.