Biomedical subjects

Y Mizuki

Publications and source records attributed to Y Mizuki.

At least 37 records · Page 2Linked to original sources

PubMed1996

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.

Adult↗

PubMed1996

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.

Adult↗

PubMed1996

Intermolecular interactions of antimicrobial fluoroquinolones with purified rat liver CYP1A2 studied by proton nuclear magnetic resonance spectroscopy.

1. Binding and inhibition of antimicrobial fluoroquinolones towards liver CYP1A2 purified from 3-methylcholanthrene-treated rats were investigated using proton nuclear magnetic resonance (nmr) and phenacetin metabolism. 2. The proton nmr longitudinal relaxation rate study indicated that the paramagnetic effects of the haem iron of CYP1A2 were observed in protons of enoxacin with a 1,8-naphthyridine skeleton and its 4'-nitrogen atom on the 7-piperazine ring probably participated in specific binding to the haem iron. These data suggest a facile accessibility and strong binding of enoxacin to the active site of the enzyme. On the contrary, the binding region of norfloxacin with a quinoline skeleton could not be specified, and an 8-fluorinated derivative (AT-3970) had much lower paramagnetic effects and no specific binding region. 3. In a reconstituted CYP1A2 system, enoxacin exhibited the most potent inhibition of phenacetin O-deethylation. The metabolism was less inhibited by norfloxacin, and AT-3970 had a weak inhibitory activity. 4. The binding ability of the fluoroquinolones to the CYP1A2 active site is likely to determine their inhibitory activity against phenacetin metabolism.

Animals↗

PubMed1995

Alteration of cataleptic responses induced by dopamine receptor antagonists after chronic cocaine administration in mice.

The influence of chronic treatment of mice with cocaine, an indirect dopamine receptor agonist, on the cataleptic effects of R-(+)-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin- 7ol hydrochloride (SCH23390), a dopamine D1 receptor antagonist, or haloperidol, mainly a dopamine D2 receptor antagonist, was investigated. Mice were given cocaine (10 mg/kg s.c.) once every other day for 7 (4 injections), 15 (8 injections) or 21 (11 injections) days. The cataleptic effects of SCH23390 (0.3 mg/kg i.p.) were significantly reduced when it was given 1-7 days after the last dose of a 7- or 15-day pretreatment course of cocaine. When SCH23390 was given 14-21 days after the cocaine the cataleptic effect was increased in the 15-day, but not the 7-day, cocaine-pretreated mice. However, after a 21-day treatment with cocaine, a challenge dose of SCH 23390 given 1-3 days thereafter produced a decreased cataleptic response, but an increased response after 7-21 days. The cataleptic effects of haloperidol (o.3 mg/kg i.p.) were reduced when it was given 1-7 days after the last dose of a 7-day pretreatment, but increased 1-3 days after that of a 15-day pretreatment with cocaine (10 mg/kg s.c.) The pretreatment with cocaine for 21 days did not affect the haloperidol catalepsy during a 1- to 3-day withdrawal period. However, haloperidol catalepsy was decreased only 7 days, then reversed 14 days and gradually increased 21 days after the last injection of a 15- or 21-day pretreatment course of cocaine. These results suggest that chronic treatment with the indirect dopamine receptor agonist, cocaine, caused supersensitivity of dopamine D1 receptors (a decrease in SCH23390 catalepsy) during the early withdrawal period and subsensitivity (an increase in SCH23390 catalepsy) after a longer period of withdrawal. It was apparent that the longer the period and the higher the dose of pretreatment with cocaine, the less were the alterations in initial responses and the greater were the alterations in subsequent responses to the dopamine D1 receptor antagonists.

Animals↗

PubMed1995

Development of tolerance and reverse tolerance to haloperidol- and SCH23390-induced cataleptic effects during withdrawal periods after long-term treatment.

The development of tolerance and reverse tolerance and reverse tolerance to the cataleptic effects of selective D1 antagonist, SCH23390, and the mainly D2 antagonist, haloperidol, was investigated in mice that had been chronically treated (7 or 30 days) with haloperidol (1 mg/kg SC), SCH23390 (0.5 mg/kg SC), or saline (5 ml/kg SC). In control animals, SCH23390 (0.1-1.0 mg/kg IP) and haloperidol (0.1-1.0 mg/kg IP) produced cataleptic responses in a dose-dependent manner, although the responses had different time course profiles. SCH23390 catalepsy had a rapid onset but a short duration, whereas haloperidol catalepsy had a slower onset and longer duration. This could be due to differences in lipid solubility of the drugs, or at least pertly to an action of the drugs on different neuronal pathways. The cataleptic effects of SCH23390 (0.3 mg/kg IP) and haloperidol (0.3 mg/kg IP) were significantly reduced in mice when given 24 h, but not 72 h, after the last dose of a 7 day-pretreatment course (short-term treatment) of SCH23390. However, after long-term treatment (30 days) with SCH23390, a challenge dose of SCH23390 exhibited reverse tolerance (i.e., increased catalepsy) when given 7-21 days, but not 1-3 days, after the last injection of the SCH23390 pretreatment course. In contrast, haloperidol catalepsy was not affected by long-term SCH23390 treatment. However, after the last dose of long-term haloperidol treatment both SCH23390 and haloperidol exhibited tolerance to their cataleptic effects at 1-3 days, a normal response at 7 days, and an exaggerated response (reverse tolerance) at 15-21 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

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.

Adult↗

PubMed1994

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.

Adult↗

PubMed1994

Comparative pharmacokinetics of the histamine H1-receptor antagonist ebastine and its active metabolite carebastine in rats, guinea pigs, dogs and monkeys.

The pharmacokinetics of ebastine (CAS 90729-43-4), a new histamine H1-receptor antagonist, was investigated in rats, guinea pigs, dogs and monkeys. Plasma levels of ebastine and its active carboxylated metabolite, carebastine (CAS 90729-42-3), were determined after an intravenous dose (2 mg/kg) or an oral dose (10 mg/kg). After intravenous administration to dogs, plasma levels of the unchanged ebastine showed a bi-phasic decrease with a t1/2 alpha of 0.16 h and t1/2 beta of 4.2 h. In contrast, after oral administration, the unchanged ebastine was scarcely detected in plasma of 4 animal species examined, indicating extensive first-pass metabolism of ebastine. There were marked interspecies differences in the plasma concentration-time profiles of carebastine after oral administration of ebastine. The Cmax of carebastine in guinea pigs (2820 ng/ml) was markedly higher than that in rats (311 ng/ml), dogs (465 ng/ml) and monkeys (1036 ng/ml). Guinea pig also showed the slower elimination of carebastine (t1/2 of 9.4 h) than rat (0.92 h), dog (2.4 h) and monkey (1.2 h). After oral administration of carebastine to rats, the Cmax and AUC were approximately 3/4 of those after administration of ebastine. Once daily 7-day repeated oral administrations of ebastine did not affect the pharmacokinetics of ebastine and carebastine in rats. These findings strongly indicate that carebastine is responsible for the antihistamine activity after oral administration of ebastine.

Administration, Oral↗

PubMed1994

[Effects of dopamine receptor agonists and antagonists on cocaine-induced behaviors in rats].

In this study, cocaine (5-20 mg/kg), an indirect dopamine agonist, increased locomotor activity and rearing accompanied with head circling and body shaking in a dose-dependent manner. A high dose of cocaine (40 mg/kg), meaning a toxic dose, slightly induced sniffing and licking. Both SCH23390, a D-1 receptor antagonist, and raclopride, a D-2 antagonist, inhibited all behaviors induced by cocaine, suggesting that the behavioral actions of cocaine may involve the activation of D-1 and D-2 receptors. Selective D-2 agonist quinpirole (0.1 and 1.0 mg/kg) inhibited hyperlocomotion induced by cocaine (20 mg/kg), but was replaced by the typical stereotyped behaviors such as sniffing at low dose (0.1 mg/kg), and licking and gnawing at high dose (1.0 mg/kg). SK & F38393, a selective D-1 agonist, in combination of cocaine did not induce these stereotyped behaviors which resulted in synergistic interaction of D-1 and D-2 receptor stimulation. These results suggest that the indirect stimulation of postsynaptic D-2 receptors by cocaine (20 mg/kg) was insufficient to induce stereotyped behaviors. The actions of cocaine on dopamine D-1 receptors seem to be more potent than that on D-2 receptors.

Animals↗

PubMed1993

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.

Cognition Disorders↗

PubMed1993

Pharmacokinetics of the gastrokinetic agent mosapride citrate after intravenous and oral administrations in rats.

The pharmacokinetics and bioavailability of mosapride citrate ((+/-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2- morpholinyl]methyl]benzamide citrate dihydrate, AS-4370, CAS 112885-42-4) were investigated in rats of both sexes. Plasma levels of mosapride and its des-4-fluorobenzyl metabolite (M-1) were determined after an intravenous dose of 2 mg/kg or an oral dose of 10 mg/kg. There were marked sex-related differences in the mean plasma concentration-time profiles of mosapride after single intravenous and oral administration. After oral administration, the Cmax of the unchanged mosapride in male rats (44 ng/ml) was approximately 1/18 of that in female rats (788 ng/ml). The Cmax of M-1 (277 ng/ml) was 6 times higher than that of mosapride in males, while the Cmax in females (149 ng/ml) was 1/5 of that of mosapride. Male rats exhibited more rapid elimination (t1/2 of 1.9 h) than females (2.8 h). These sex-dependent pharmacokinetics of mosapride in rats would be explained by two reasons: different activity of hepatic drug-metabolizing enzymes to M-1 and partly different distribution volume of mosapride. Oral bioavailability of mosapride was 7% of the dose in males and 47% in females, suggesting extensive first-pass metabolism in males. Once daily 7-day multiple administration did not affect the pharmacokinetics of mosapride both in male and female rats.

Administration, Oral↗

PubMed1993

Pharmacokinetics of the gastrokinetic agent mosapride citrate after intravenous and oral administrations in dogs and monkeys.

The pharmacokinetics and bioavailability of mosapride citrate ((+-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4- fluorobenzyl)-2-morpholinyl]methyl]benzamide citrate dihydrate, AS-4370, CAS 112885-42-4), a new gastrokinetic agent, were investigated in dogs and monkeys. Plasma levels of mosapride and its des-4-fluorobenzyl metabolite (M-1) were determined after a single intravenous dose (2 mg/kg) or a single oral dose (10 mg/kg). After intravenous administration, mean plasma levels of mosapride in male dogs and monkeys showed biphasic decrease with t1/2 alpha of 0.3 and 0.6 h, and t1/2 beta of 2.4 and 2.4 h, respectively. Mean concentrations of mosapride increased rapidly and reached the maximum 0.5-1 h after oral administration to male dogs and monkeys, followed by quick decrease with t1/2 of 1.5 and 0.9 h, respectively. The Cmax was 207 ng/ml in dogs and 862 ng/ml in monkeys. The Cmaxs of M-1 in both species were virtually equivalent to those of the unchanged drug. Plasma concentration-time profiles and pharmacokinetic parameters of mosapride and M-1 in female dogs and monkeys were similar to those in males, indicating no sex-related differences in the pharmacokinetics of mosapride in these animal species. Oral bioavailability was 8% of the dose in dogs and 14% in monkeys, suggesting the extensive first-pass metabolism of mosapride.

Administration, Oral↗

PubMed1992

Effects of lithium and purinergic compounds on the behavioral and physiological aspects of restraint stress in rats.

This study investigates the effects of lithium and caffeine on psychomotor activities, defecation, and gastric lesions induced by restraint stress. Rats exposed to restraint stress typically exhibited a biphasic response consisting of an initial hypermotility (such as tail-flipping, body-rolling, jaw movement, and vocalization) accompanied by defecation, and followed by hypomotility (decrease in motility) accompanied by gastric ulceration. Lithium chloride (150 micrograms, ICV; 50 and 100 mg/kg, IP) significantly attenuated these responses while N6-cyclohexyl adenosine (CHA; 1.5 micrograms, ICV; 0.3 mg/kg, IP), a potent adenosine A1 receptor agonist, attenuated the behavioral effects but potentiated the gastric ulceration. Caffeine (3 micrograms, ICV; 1.0 mg/kg, IP), an adenosine receptor antagonist, inhibited the effects of CHA in animals exposed to 3 h of stress, but aggravated the effects in animals exposed to 6-12 h of stress. These results suggest that caffeine consumption may produce supersensitivity of adenosine receptors, which potentiate the actions of adenosine or CHA. Lithium may modulate the effects of stress by indirectly inhibiting central adenosine receptor activity.

Adenosine↗

PubMed1992

Behavioral effects of dilazep on cholinergic, dopaminergic, and purinergic systems in the rat.

This study examined the effects of 1,4-bis[3-(3,4,5-trimethoxy benzoyloxy)-propyl] perhydro-1,4-diazepine (dilazep; Comelian) on central dopaminergic, cholinergic, and purinergic neuronal systems in rats. Intraperitoneal injections of dilazep (1-5 mg/kg) produced yawning responses, the most effective dose being 2 mg/kg. Dilazep potentiated physostigmine-induced yawning but not pilocarpine- and bromocriptine-induced yawning. Dilazep-induced yawning was not affected by low doses of haloperidol or sulpiride, but was completely inhibited by atropine, a muscarinic M1 receptor antagonist. Dilazep-induced yawning, as well as physostigmine-induced yawning, were markedly inhibited by pretreatment with SK & F 38393, a dopamine D1 receptor agonist, and were potentiated by SCH23390, a dopamine D1 receptor antagonist that alone does not elicit yawning. Caffeine, an adenosine receptor antagonist, inhibited dilazep- and physostigmine-induced yawning responses but N6-cyclohexyl adenosine (CHA) and N6-(L-phenylisopropyl, adenosine (L-PIA), adenosine A1 receptor agonists, were inactive. These results suggest that because the effects of dilazep on central cholinergic neurons are similar to those of physostigmine dilazep may potentiate indirectly the action of endogenous acetylcholine. Cholinergic neurons activated by dilazep may be modulated by postsynaptic dopamine D1 receptor activity but may not be affected by dopamine D2 receptor activity. Furthermore, the stimulatory effects of dilazep on cholinergic neuron may not be due to an inhibition of dopamine D1 receptors via purinergic (adenosine A1 receptor) stimulation by dilazep.

Animals↗

PubMed1992

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.

Adult↗

PubMed1992

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.

Adult↗

PubMed1992

[The threshold lowering effects of chronic treatment with haloperidol on beta-carboline derivative-induced tonic convulsion].

To clarify a relationship between dopamine neuron and purine, GABA or benzodiazepine system, we have studied the changes in the threshold of tonic convulsion induced by each antagonist after chronic treatment with haloperidol in mice. Mice were given haloperidol (1 mg/kg, sc) once a day for 19 d and challenged with caffeine (an adenosine receptor antagonist), beta-DMCM (beta-carboline derivative: as a benzodiazepine receptor antagonist), picrotoxin (a Cl- channel blocker) or bicuculline (a GABAa receptor antagonist) 30 min, 24 h and 48 h after the last injection of haloperidol. Only the threshold of beta-DMCM-induced tonic convulsion was lowered and it was reversed 7 d after the last injection. The beta-DMCM-induced convulsions on 2 d withdrawal were reversed by diazepam (2.5 mg/kg, ip; a benzodiazepine receptor agonist), Ro15-1788 (5.0 mg/kg, ip; as like a benzodiazepine receptor partial agonist), muscimol (2.0 mg/kg, ip; a GABAa receptor agonist) or apomorphine (0.25 and 2.0 mg/kg, ip; a dopamine receptor agonist). These results suggest that the lowering effect of chronic haloperidol on seizure threshold may be involved in the development of tolerance to haloperidol. It may implicate in direct interactions between benzodiazepine and dopamine or GABA systems but may not between dopamine and GABA neurons in development of lowering seizure threshold following chronic haloperidol treatment.

Animals↗

PubMed1991

Psychological stress increases dopamine turnover selectively in mesoprefrontal dopamine neurons of rats: reversal by diazepam.

The effects of psychological stress on catecholamine and indoleamine metabolism were examined in various brain regions of rats. Psychologically stressed rats were exposed to emotional responses of foot-shocked rats, but were themselves prevented from receiving foot-shock. Psychological stress for 30 min resulted in significant increases of both 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in the medial prefrontal cortex (MPFC), but not in other dopamine (DA) terminal fields. The levels of noradrenaline (NA), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were unaffected in all brain regions examined after 30 min of psychological stress. A small but significant increase of DOPAC levels in the ventral tegmental area (VTA) was observed after a shorter (10 min) duration of stress. Moreover, an increase of DOPAC levels in the MPFC 30 min after psychological stress was attenuated by diazepam (5 mg/kg), and this attenuating effect was antagonized by Ro 15-1788 (15 mg/kg). These results suggest that mesoprefrontal DA neurons are selectively activated by psychological stress, and that the activation of the A10 cell body site (VTA) may precede that of the terminal field (MPFC). Moreover, diazepam was found to possess an inhibitory effect on the activation of mesoprefrontal DA neurons induced by psychological stress, and this effect may be partly mediated by benzodiazepine (BZD) receptors and implicated in the specific anxiolytic action of BZDs.

3,4-Dihydroxyphenylacetic Acid↗