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Biomedical subjects

S Ueki

Publications and source records attributed to S Ueki.

At least 73 records · Page 4Linked to original sources

Effects of benzodiazepine and GABA antagonists on anticonflict effects of antianxiety drugs injected into the rat amygdala in a water-lick suppression test.

In order to elucidate the role of the amygdala in rat conflict behavior in a water lick suppression test, we examined the effect of lesions of various nuclei of the amygdaloid complex on this behavior. An anticonflict effect was produced by a lesion of the anterior part of central and basolateral amygdala, and lesion to the posterior part of the central amygdala, but not by posterior of the basolateral amygdala or medial amygdala lesions. These results suggest that the amygdala, especially the anterior part of the central and basolateral nuclei, plays an important role in conflicting behavior of rats in the water lick test. In a second experiment, the effects of benzodiazepine- and GABA-antagonists on the anticonflict action of diazepam, zopiclone, and phenobarbital injected into the anterior part of central and basolateral amygdala were examined, also using a water lick suppression test. A dose-dependent anticonflict action was produced by systemic administration as well as by intra-amygdala injection of diazepam, zopiclone, lormetazepam, flurazepam and phenobarbital. The order of potency was lormetazepam greater than zopiclone greater than or equal to diazepam greater than flurazepam greater than or equal to phenobarbital for both routes of injection. The anticonflict effects of diazepam and zopiclone injected into the amygdala were completely reversed by Ro15-1788 and beta-CCM but not by bicuculline, while the anticonflict effect of phenobarbital was reversed by beta-CCM but not by Ro15-1788 or bicuculline. The present results strongly suggest that the anterior nuclei of central and basolateral amygdala are important sites of action of antianxiety drugs, and that an anticonflict action produced by intra-amygdala injection of benzodiazepines or barbiturate is mediated through the different receptor mechanisms.

Amygdala↗

Inhibitory effect of a selective kappa receptor agonist, U-50, 488H, on methamphetamine-elicited ipsilateral circling behavior in rats with unilateral nigral lesions.

The present study was designed to investigate the effect of U-50, 488H, a highly selective kappa opioid agonist, on ipsilateral and contralateral circling behavior induced by methamphetamine and by apomorphine, respectively. U-50, 488H (3.2-10 mg/kg IP) by itself failed to induce either ipsilateral or contralateral circling in rats with unilateral nigral lesions produced by an injection of 6-hydroxydopamine. U-50, 488H produced a significant dose-dependent inhibition of methamphetamine (1.0 mg/kg SC)-elicited ipsilateral circling. However, it had no effect on contralateral circling induced by apomorphine (0.5 mg/kg SC). The present results indicate that U-50, 488H presynaptically inhibits the release of dopamine in the rat striatum.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Conflict behavior and dynamics of monoamines of various brain nuclei in rats.

The present study was an attempt to clarify the role of noradrenaline (NA) and of the 5-hydroxytryptamine (5-HT) system in various nuclei in brain, as a component of a proposed neural circuit in the mediation of conflict behavior and the anticonflict action of anxiolytics. The authors investigated changes in the concentrations of NA, 3-methoxy-4-hydroxyphenylethyleneglycol, 5-HT and 5-hydroxyindoleacetic acid in discrete regions of the brain in rats, in correlation with conflict behavior and also the effects of diazepam and suriclone. Noradrenergic neural activity diminished with a conflict situation, in the frontal cortex, central amygdala, mammillary body and dorsal hippocampus. 5-Hydroxytryptaminergic neural activity increased with a conflict situation in the frontal cortex, central amygdala, basolateral amygdala and medial septum. These changes in the frontal cortex, central amygdala, mammillary body and dorsal hippocampus were not observed when diazepam 20 mg/kg (p.o.) and suriclone 40 mg/kg (p.o.) produced anticonflict action. Suriclone normalized the increased 5-HT-ergic activity in the medial septum. The suppression of NA-ergic and the activation of 5-HT-ergic (except for the mammillary body) neural activity in the frontal cortex, central amygdala, mammillary body and dorsal hippocampus seemed to be linked to the mediation of conflict behavior. The facilitatory and inhibitory action on NA and 5-HT (except for the mammillary body) neurons, respectively, in these regions of the brain, may be involved in mechanisms underlying the anticonflict action of anxiolytics (diazepam or suriclone).

Animals↗

Effect of bilateral septal lesions on discrimination avoidance conditioning in rats.

Studies were performed, using the two-way shuttle box method, on the acquisition of discrimination avoidance by rats with bilateral lesions of the septum (septal rats) in relation to changes in emotional behavior. Septal rats exhibited hyperreactivity immediately after the lesions were made: their startle, struggle and vocalization responses to stimuli were markedly increased. These hyperemotional responses, however, decreased and returned to the normal level 7 days after surgery. Initially, the septal rats showed elevated conditioned avoidance responses to both the CS+ and the CS-. In later stages, their responses to the CS+ showed progressive and gradual increase, accompanied by a decrease in responses to the CS-, until responses to both stimuli were only slightly elevated above the level of control rats. These results suggest that bilateral lesions of the septum do not affect discrimination ability itself. The impairment of discrimination avoidance during the initial stages may result from the transient impairment of the discrimination acquisition process.

Animals↗

In vivo changes in brain catecholamine release from rat hypothalamus following olfactory bulbectomy.

The mechanism eliciting mouse-killing behavior (muricide), induced by bilateral olfactory bulbectomy, has been shown to involve the brain noradrenergic system; this is because muricide is specifically inhibited by the drugs which potentiate the activity of catecholaminergic neurons such as tricyclic antidepressants. Our previous reports also demonstrated that the hypothalamic noradrenaline (NA) contents increased in the rats which exhibited muricide. To further examine the hypothalamic noradrenergic function in muricide, a push-pull perfusion technique was applied for direct measurement of NA release from the lateral (LH) and ventromedial (VMH) hypothalamus in freely moving rats. Subsequently, the perfusates, including catecholamines and their metabolites were measured by means of high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Three days after olfactory bulbectomy, 67% of the rats elicited muricide and NA release from LH tended to decrease. Moreover, 7 days after olfactory bulbectomy, most of the rats elicited muricide and NA release from LH was significantly decreased, but not from VMH. On the other hand, dopamine (DA) release from VMH without LH conversely increased on the 7th day after olfactory bulbectomy. These results suggest that the dysfunction of the noradrenergic system caused by the decrease in NA release from LH played an important role for the incidence of muricide.

Animals↗

Inhibition of mouse-killing behavior by S-adenosyl-L-methionine in midbrain raphe-lesioned and olfactory-bulbectomized rats.

The effect of S-adenosyl-L-methionine (SAM), a methyl donor, on mouse-killing behavior in rats with lesions of the midbrain raphe nuclei and in olfactory-bulbectomized rats was investigated. Systemic administration of SAM at doses of 180 and 320 mg/kg IP caused a significant inhibition of both kinds of mouse-killing behavior. The inhibitory effects of SAM on both types of mouse-killing behavior were almost equipotent. Microinjection of SAM at 10-100 micrograms/rat into the lateral ventricle also inhibited mouse-killing behavior induced by raphe lesions in a dose-dependent manner. The ED50 value of SAM for this effect was 38.6 (18.4-81.4) micrograms/rat. It is concluded that SAM has inhibitory effects on mouse-killing behavior in both raphe-lesioned and olfactory-bulbectomized rats through a site of action in the central nervous system.

Animals↗

Relative importance of the dopaminergic system in haloperidol-catalepsy and the anticataleptic effect of antidepressants and methamphetamine in rats.

The mechanisms involved in haloperidol (HPD)-catalepsy in rat and the effect of antidepressants and methamphetamine (MA) were studied. HPD-catalepsy, as measured by high bar test, lasted for 6-8 min. MA, imipramine (IMP), nomifensine (NOM) and mianserin (MIAN) reduced the duration of catalepsy on IP injection. Electrolytic lesion of the caudate-putamen (CP) and nucleus accumbens (ACC) extensively reduced HPD-catalepsy. Microinjection of MA and NOM into ACC had a similar effect. In the medial amygdala and CP, only MA displayed anticataleptic activity. Zimelidine did not reduce the duration of catalepsy. These results suggest that dopaminergic systems play a key role in mediating HPD-catalepsy and the anticataleptic activity of MA and NOM.

Animals↗

Delta 9-tetrahydrocannabinol facilitates striatal dopaminergic transmission.

We examined the effects of delta 9-tetrahydrocannabinol (THC) on striatal dopaminergic neurons in rats. THC inhibited the uptake of 3H-dopamine (DA) into striatal synaptosomes. THC facilitated the release of endogenous DA but not dihydroxyphenylacetic acid (DOPAC) from striatal slices. The concentration of DA in the dorsolateral striatum was reduced by THC. We propose that THC may stimulate nigrostriatal dopaminergic neurotransmission mainly by inhibiting uptake of DA and by facilitating release of DA.

3,4-Dihydroxyphenylacetic Acid↗

Experience with the ultrasonic surgical aspirator in a cavernous hemangioma of the cavernous sinus.

A patient with a cavernous hemangioma of the cavernous sinus was operated upon using the Cavitron Ultrasonic Surgical Aspirator (CUSA). Intracapsular subtotal removal of the tumor was accomplished efficiently with the CUSA. At the end of the procedure, however, the CUSA penetrated not only the capsule of the tumor, but also the wall of the internal carotid artery. Advantages and disadvantages of CUSA surgery for cavernous hemangiomas of the cavernous sinus are discussed.

Adult↗

Behavioral and electroencephalographic effects of a depot type neuroleptic fluphenazine decanoate, in rats.

The behavioral and electroencephalographic (EEG) effects of intramuscular fluphenazine decanoate (Fl-D) were investigated in rats and compared with those of fluphenazine enanthate (Fl-E) and fluphenazine HCl (Fl-HCl). It was clearly observed that 1) these two depot type neuroleptics reduced open-field activity, 2) antagonized methamphetamine-induced hyperactivity, 3) inhibited the conditioned avoidance response, and 4) produced catalepsy, for a substantially long period of time (4-35 d). Although both Fl-D and Fl-E significantly inhibited muricide in olfactory bulbectomized rats and impaired rotarod performance, these effects were relatively weak in potency and short-lasting (4 h-2 d). The EEG was changed to a drowsy pattern which consisted of high voltage slow waves following the injection of Fl-D and Fl-E. Fl-D significantly inhibited the EEG arousal response to auditory stimulation, but Fl-E did not. However, neither Fl-D nor Fl-E inhibited the EEG arousal response to electrical stimulation of the midbrain reticular formation and posterior hypothalamus. These results indicate that Fl-D has the same spectrum of pharmacological activity as Fl-E, except for its longer duration of action in antagonizing methamphetamine as well as in inhibiting the EEG arousal response to auditory stimulation.

Acoustic Stimulation↗

[Behavioral pharmacological properties of the novel antidepressant paroxetine, a selective 5-HT uptake inhibitor].

The behavioral effects of paroxetine were investigated in mice and rats in comparison with imipramine and amitriptyline. 1) Locomotor activities were decreased by imipramine and amitriptyline but not by paroxetine in both animal species. 2) Paroxetine antagonized methamphetamine-induced hyperactivity in mice as did imipramine and amitriptyline. 3) Paroxetine showed a more potent antimuricidal effect in raphe-lesioned rats than imipramine and amitriptyline, and it also inhibited muricide in olfactory bulbectomized rats. 4) The immobility of rats in the forced swimming test was markedly decreased by imipramine and amitriptyline, but only slightly by paroxetine. 5) Like imipramine and amitriptyline, paroxetine potentiated the methamphetamine- or L-DOPA-induced stereotyped sniffing, and it inhibited oxotremorine-induced tremor. 6) Paroxetine antagonized reserpine-induced hypothermia, tetrabenazine-induced ptosis, and enhanced ether-induced anesthesia, all less potently than imipramine and amitriptyline. 7) The analgesic action of paroxetine was stronger than that of imipramine and amitriptyline. 8) Paroxetine did not antagonize maximal electroshock- or pentetrazol-induced convulsions and haloperidol- or THC-induced catalepsy in rats. In addition, paroxetine neither exerted muscle relaxation nor affected the shuttle-box type conditioned avoidance in rats. From these results, the behavioral effects of paroxetine, as compared with imipramine and amitriptyline, were characterized by its potent antimuricidal action in raphe-lesioned rats and its weak effect in the forced swimming test and by its less potent muscle relaxant, anticonvulsant, anticataleptic and anesthesia-potentiating actions.

Aggression↗

Effect of isofloxythepin, a novel neuroleptic, on hippocampal stimulation-induced wet-dog shaking in the rat.

(+/-)Isofloxythepin (0.32-3.2 mg/kg, i.p.) significantly inhibited in a dose-dependent manner wet-dog shaking (WDS) induced by electrical stimulation of the rat hippocampus. In addition, both optical isomers of isofloxythepin inhibited WDS, with the (-)-isomer being almost 3 times more potent than the (+)-isomer. Other neuroleptics such as haloperidol, chlorpromazine, zotepine and sulpiride also reduced significantly the number of WDS. The inhibitory potency of haloperidol was comparable to that of (+/-)isofloxythepin, which was approximately 3 times more potent than that of chlorpromazine or zotepine. Sulpiride suppressed significantly WDS only at the high dose of 100 mg/kg. None of the drugs affected hippocampal afterdischarge. Inhibition of WDS produced by (+/-) isofloxythepin or haloperidol was antagonized by pretreatment with a dopamine receptor agonist, lisuride. The present results indicate that isofloxythepin shares with other neuroleptics an inhibitory effect on WDS; dopaminergic blocking action appears to be important in the inhibition of WDS induced by hippocampal stimulation.

Animals↗

Behavioral analysis of zopiclone on the basis of their discriminative stimulus properties in the rat.

Zopiclone is a new cyclopyrrolone derivative which exerts pharmacological activities similar to those of benzodiazepines in behavioral and biochemical studies. In order to clarify the discriminative stimulus properties of zopiclone, 8 rats were trained to discriminate the interoceptive stimulus induced by zopiclone (3.2 mg/kg, i.p.) from those of saline. Following discrimination acquisition, administration of zopiclone resulted in drug-appropriate responding with an ED50 of 1.3 (1.0-1.8) mg/kg. The zopiclone discriminative stimulus generalized to the benzodiazepines diazepam (1.8 mg/kg), nitrazepam (10 mg/kg) and alprazolam (10 mg/kg). A non-benzodiazepine, suriclone, at 3.2 mg/kg, generalized to the zopiclone stimulus in 5 out of 7 rats, but meprobamate, hydroxyzine, tracazolate and muscimol did not. The benzodiazepine antagonist Ro 15-1788 (1 mg/kg) completely blocked zopiclone stimulus. In contrast, however, bicuculline and pentetrazol failed to antagonize it. The serotonin antagonist cinanserin and ritanserin neither generalized to the zopiclone stimulus nor did they exhibit antagonism. These results suggest that the zopiclone discriminative stimulus is mediated by binding to benzodiazepine receptors and appears not to be related to GABAergic or serotonergic system.

Animals↗

A key role of the mammillary body in mediation of the antianxiety action of zopiclone, a cyclopyrrolone derivative.

The present study was designed to elucidate the brain site of the anticonflict action of zopiclone (ZOP), a cyclopyrrolone derivative, using the rat conflict procedure. ZOP at 10 micrograms/microliters, bilaterally injected into the mammillary body (MB), produced a significant increase in the punished responses, with no change in the unpunished responses. There were no significant changes in these responses when ZOP was injected into the central amygdala, frontal cortex or dorsal hippocampus. Attention should be given to the possibility that the MB is the site of the anticonflict action of ZOP.

Animals↗

Effect of Z-103 on compound 48/80-induced gastric lesions in rats.

Z-103 (a novel anti-ulcer agent), given p.o. at doses of 30 and 100 mg/kg, significantly prevented gastric lesions induced by compound 48/80 in rats. Z-103 inhibited the histamine release from rat peritoneal mast cells stimulated by compound 48/80 in a dose-dependent manner. Z-103 inhibited the increase in thiobarbituric acid (TBA) reactants induced by a single or repeated administration of compound 48/80 in the gastric mucosa. These observations suggested that the protective effect of Z-103 against compound 48/80-induced gastric lesions may be due to its stabilizing activity toward mast cells and/or an antioxidative effect on the gastric mucosa.

Animals↗

[Human papilloma virus (HPV) antigens and DNA in dysplasia and carcinoma of the uterine cervix].

Routinely paraffin-embedded sections of dysplasia, carcinoma in situ (CIS) and invasive (squamous) carcinoma of the cervix were studied to determine the participation of human papilloma virus (HPV) in these tissues. Morphological observation (1,059 cases) revealed condylomatous changes to reach 54% in dysplasia, 25% in CIS and 25% in invasive carcinoma. Condylomatous changes were also found to be 25 to 40% in the non-cancerous epithelia adjacent to in situ or invasive carcinomas. The immuno-peroxidase-PAP-method using anti-HPV serum was applied to 98 selected sections in which condylomatous changes were morphologically observed. HPV antigens were found to reach 56% in dysplasia, 42% in CIS and 35% in invasive carcinoma, and this result suggested that the morphologically observed condylomatous changes did not always coincide with virus maturation in the infected cells. By means of the in situ hybridization technique, HPV type-6, -11, -16 and -18 DNAs were all detected in dysplasia sections, whereas HPV type-16 DNA was demonstrated distinctively at a high rate among in situ and invasive carcinomas.

Antigens, Viral↗

[Estrogen production in epithelial tumors of the ovary--clinical and endocrinological study in postmenopausal women].

Estrogen-producing activity of common epithelial tumors (54 cases) and metastatic tumors (4 cases) of the ovary was clinically and endocrinologically studied in postmenopausal patients. High serum concentrations of E1 (greater than or equal to 50 pg/ml) and E2 (greater than or equal to 30 pg/ml) were demonstrated in 78% in the group of postmenopausal patients. Mucinous tumors were more commonly associated with high estrogen levels than serous tumors. Patients with malignant tumors more frequently have a high level of serum estrogen than those with benign tumors. Estrogen decreased to normal after complete resection of the tumor, but returned to the abnormal range following a recurrence. The local-peripheral gradient of the estrogen level was noted by measuring the estrogen concentration in the blood of the affected ovarian and peripheral veins at the time of laparotomy. These results indicated that serum estrogen in the patient was originally produced in the ovarian tumor mass. The increased estrogen were reflected in such target tissues as the endometrium and vaginal mucosa. Proliferation, hyperplasia, atypical hyperplasia and even a case of carcinoma of the endometrium were observed in patients with ovarian tumors. An increase in the karyopyknotic index (KPI) of the vaginal smear, as well as uterine bleeding, could be an important signs of asymptomatic ovarian tumors in postmenopausal women.

Biomarkers, Tumor↗

Fine structure of cartilage elastic system fibers, in particular those of the mandibular condyle.

Light microscopy of the mandibular joint tissues from fetal mice show a distribution of fibrillar structures in the articular fibrous capsule covering the condylar head. Further SEM and TEM studies were conducted on autoclaved xiphoid and mandibular condylar processes of the fetuses for observation of the elastic system fibers in these cartilaginous tissues. SEM showed that non-collaginous fibers branched and united to form a complicated network in the cartilage. A fine structure study on diameter distribution of the fibers indicated elastogenesis in the differentiating cell layer and fiber maturation in the articular surfaces and calcification layer, thus suggesting a sequential development, growth, and degeneration of the cellular and fibrillar components in the cartilage, as well as bidirectional cell differentiation in the growing mandibular joint. A further TEM study on these autoclaved connective tissues showed the elastic system fibers in the network to be composed of fine microfibrils and amorphous elastin. The elastic fibers in the condylar cartilage were a loose network having many tortuous main and oblique elastic fibers, and coiling oxytalan fibers.

Animals↗