PubMed Health⌕ Search

Biomedical subjects

S Otsuki

Publications and source records attributed to S Otsuki.

At least 37 records · Page 2Linked to original sources
PubMed1992

Long-lasting enhancement of metabotropic excitatory amino acid receptor-mediated polyphosphoinositide hydrolysis in the amygdala/pyriform cortex of deep prepiriform cortical kindled rats.

We have previously demonstrated that ibotenate (IBO)-stimulated polyphosphoinositide (PPI) hydrolysis is increased for a long period in the amygdala/pyriform cortex (AM/PC) of amygdala (AM)- and hippocampal (HIPP)-kindled rats. This finding indicates that enhanced function of the PPI-coupled excitatory amino acid (EAA) receptor may be associated with the long-lasting seizure susceptibility of kindling. The present study further examined PPI hydrolysis induced by trans-ACPD, a selective agonist of the metabotropic EAA receptor, as well as by IBO in brain slices of rats kindled from the deep prepiriform cortex (DPC). IBO-stimulated accumulation of [3H]inositol monophosphate ([3H]InsP) was significantly increased in the AM/PC by 162 (P less than 0.0001), 130 (P less than 0.005) and 81% (P less than 0.03) at 24 h, 7 days and 28 days, respectively, after the last kindled seizure, whereas it was increased significantly only at 24 h after the last seizure in the HIPP and did not change at any time in the limbic forebrain (LFB). The IBO-stimulated accumulation of [3H]InsP was significantly increased by 55% (P less than 0.01) in the AM/PC of partially kindled rats reaching an average stage of 3.7, but not in the AM/PC of those remaining at stage 1, 7 days after the last kindled seizure. Trans-ACPD-stimulated PPI hydrolysis was significantly increased in the AM/PC of DPC-kindled rats by 65 (P less than 0.05) and 45% (P less than 0.005) at 7 and 28 days, respectively, after the last kindled seizure. Cis-ACPD-stimulated PPI hydrolysis was also significantly increased in the AM/PC of DPC-kindled rats by 45 (P less than 0.03) and 30% (P less than 0.04) at 7 and 28 days, respectively, after the last seizure. There was no increase in trans-ACPD- or cis-ACPD-stimulated PPI hydrolysis in the HIPP or LFB. These results further confirm our previous studies showing that the metabotropic EAA receptor-stimulated PPI hydrolysis exhibited a long-lasting increase in the AM/PC irrespective of the primary stimulation site for kindling.

Amygdala↗
PubMed1992

BMY-14802 reverses the reduction of striatal dopamine release induced by (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine.

Intraperitoneal injection of (+)-3-[3-hydroxyphenyl)-N-(1-propyl)piperidine ((+)-3PPP), a sigma receptor agonist, significantly reduced the striatal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) measured by in vivo microdialysis. These reductions were significantly greater at (+)-3PPP doses of 12 and 24 mg/kg than at 1 mg/kg. The levels of 5-hydroxyindoleacetic acid (5HIAA) were increased by the injection of (+)-3PPP in dose of 24 mg/kg, but were not affected at lower doses. BMY-14802, a sigma antagonist, alone at doses of 15 mg/kg and 30 mg/kg did not affect the levels of DA, DOPAC, HVA and 5HIAA. Pretreatment with 30 mg/kg BMY-14802 reversed the reduction of the levels of DA induced by 12 mg/kg (+)-3PPP. Although neither 30 mg/kg BMY-14802 nor 12 mg/kg (+)-3PPP affected the levels of striatal 5HIAA, combined treatment with both produced a significant elevation. These findings clearly demonstrate that sigma receptors may regulate DA release from the striatal presynapse.

Animals↗
PubMed1992

Supersensitivity of sigma receptors after repeated administration of cocaine.

We investigated the role of sigma receptors in the expression of behavioral sensitization induced by cocaine. Rats received intraperitoneal injections of either 20 mg/kg cocaine or saline once daily for 14 consecutive days. Cocaine-treated rats became sensitized. After a 5-day abstinence period, a challenge dose of (+)-3-[3-hydroxyphenyl]-N-(1-propyl)piperidine ((+)-3-PPP), a sigma receptor agonist, was administered. (+)-3-PPP at doses of 12 and 24 mg/kg induced significantly more frequent rearing and more potent stereotypy consisting of repetitive head movement and sniffing in cocaine-sensitized rats than in saline-pretreated rats. These enhanced responses to (+)-3-PPP lasted for at least a month. The enhanced responses to (+)-3-PPP were attenuated by 30 mg/kg BMY 14802, a putative sigma antagonist, and also attenuated by 100 mg/kg (+/-)-sulpiride, a D2 dopamine antagonist. These findings show that repeated administration of cocaine produces lasting supersensitivity of simga receptors, which may induce subsequent activation of dopaminergic transmission.

Animals↗
PubMed1992

Competitive and non-competitive N-methyl-D-aspartate antagonists fail to prevent the induction of methamphetamine-induced sensitization.

In order to elucidate the possible roles of the glutamate system in the mechanisms underlying behavioral sensitization, which is used as an animal model for human psychosis, we investigated the effects of 3-((+/-)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and MK-801 ((+)-dizocilpine), a competitive and noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, respectively, on methamphetamine-induced behavioral sensitization in rats. Administration of 0.5 mg/kg MK-801 enhanced 2 mg/kg methamphetamine-induced hyperactivity, whereas it reduced 6 mg/kg methamphetamine-induced stereotyped behavior markedly. CPP (10 mg/kg) reduced 2 mg/kg methamphetamine-induced stereotypy slightly. Repeated treatment with 2 and 6 mg/kg methamphetamine alone induced progressive augmentation of stereotypy, whereas combining either MK-801 or CPP with methamphetamine treatment abolished or attenuated this augmentation. However, when rats were challenged with methamphetamine after a 7-day period of abstinence, the intensity of stereotypy among the rats pretreated with repeated doses of methamphetamine alone or in combination with MK-801 or CPP did not differ significantly. These results indicate that competitive and non-competitive NMDA receptor antagonists modulate acute methamphetamine-induced abnormal behavior and sensitization expression, but they failed to prevent the induction of the neural mechanisms underlying behavioral sensitization.

Animals↗
PubMed1992

Sigma (sigma) antagonist BMY 14802 prevents methamphetamine-induced sensitization.

We have demonstrated for the first time that the sigma antagonist BMY 14802 prevents the development of behavioral sensitization induced by repeated administration of methamphetamine. Rats received an intraperitoneal injection of 15 or 30 mg/kg BMY 14802 followed by 2 mg/kg methamphetamine 30 min later. Unlike dopamine antagonists, BMY 14802 did not induce major changes in the acute motor effects of 2 mg/kg methamphetamine. Repeated administration of methamphetamine induced progressive augmentation of stereotyped behaviors and resulted in behavioral sensitization. However, repeated administration of methamphetamine in combination with BMY 14802 at either dose produced no increase in the intensity of stereotypy when compared with the first treatment. After a 7-day abstinence period, a challenge test with methamphetamine alone revealed supersensitivity of methamphetamine-sensitized rats to subsequent methamphetamine, whereas rats pretreated with repeated methamphetamine in combination with BMY 14802 exhibited no difference in the intensity of stereotypy from rats pretreated with repeated saline. These results suggest that sigma receptors play a crucial role in the induction of methamphetamine-induced sensitization.

Animals↗
PubMed1992

Voluntary intake of alcohol is attenuated by ipsapirone in mice and role of 5-HT1A receptor.

Emerging evidences have suggested that the brain serotonin (5-hydroxytryptamine, 5-HT) neurotransmitter system is involved in the compulsive alcohol-seeking behaviors in humans and animal models. The aim of this study is to examine the effect of ipsapirone, which is a specific 5-HT1A agonist with a pyrimidinylpiperazine structure, on alcohol consumption in mice (C57BL/6J) by a voluntary alcohol intake paradigm. When the consumed alcohol was expressed as g/kg B.W., the total 12-day amount was significantly lower in the ipsapirone-treated mice than in the saline-treated mice. However, 5-HT1A receptor binding sites labeled with [3H]8-OH-DPAT in hippocampal membranes did not differ significantly in either the total number of binding sites (Bmax) or dissociation constant (Kd) between the two groups. The possible mechanism regarding the role of ipsapirone that attenuated the alcohol consumption, and its relationship to the subtyping 5-HT receptors are further discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Synaptosomal membrane fluidity, lipid peroxidation and superoxide dismutase activity in the brain of amygdala-kindled rats.

Synaptosomal membrane fluidity, lipid peroxide (LPO) and cytosolic superoxide dismutase (SOD) activity were examined in various brain regions (amygdala, hippocampus, striatum and frontal cortex) of amygdala-kindled rats. At 24 h after the last seizure, a significant increase of membrane fluidity was observed in all the regions examined, whereas the LPO level was significantly decreased in the four regions with enhanced activity of cytosolic SOD. At 7 days after the last seizure, membrane fluidity was decreased only in the hippocampus. At 6 weeks after the last seizure, there were no changes in membrane fluidity between control and kindled rats. These results suggest that membrane fluidity and lipid peroxidation are modulated transiently by a kindled seizure, but not at a steady state of kindling with enduring seizure susceptibility.

Amygdala↗
PubMed1992

Lack of effect of haloperidol or methamphetamine treatment on the mRNA levels of two dopamine D2 receptor isoforms in rat brain.

In order to investigate whether changes of the two mRNAs encoding the D2 receptor isoforms were induced by chronic haloperidol or methamphetamine treatment in rats, we measured the brain mRNA levels using in situ hybridization histochemistry (ISHH). We used two oligonucleotide probes, an "insert" probe to hybridize with the longer D2 receptor, D2(444), mRNA, and a "spanning" probe to hybridize with the shorter D2 receptor, D2(415), mRNA. Both D2 mRNAs were detected by ISHH in the caudate putamen, nucleus accumbens, substantia nigra, pars compacta and ventral tegmental area. The distributions and the amounts of the mRNAs for the two D2 isoforms did not change after chronic administration of haloperidol (1 mg/kg/day for 14 days, ip) or methamphetamine (4 mg/kg/day for 14 days, ip). These results suggest that the changes of D2 receptor density induced by chronic neuroleptic and psychostimulant treatment are not due primarily to receptor expression.

Animals↗
PubMed1992

Mechanisms in the development of limbic status epilepticus and hippocampal neuron loss: an experimental study in a model of status epilepticus induced by kindling-like electrical stimulation of the deep prepyriform cortex in rats.

A new model of status epilepticus (SE), which was induced by intermittent electrical stimulation (20 Hz for 20 sec every min for 180 min) of the deep prepyriform cortex, has been developed in the conscious rat. SE was induced in 9 of 16 rats in the drug-free group. The number of stimulation trains required to induce SE in this status subgroup was 125.6 +/- 12.7 (mean +/- SEM) and the mean duration of self-sustained seizure activity (SSSA) occurring after cessation of the stimulation session was 295.4 +/- 111.4 min. Some animals showed secondary generalized seizures. Significant cell loss was observed in the hippocampal CA3 pyramidal cell layer ipsilateral to the stimulation site and bilateral CA1 areas in the status subgroup compared with the group subjected to sham operation. In addition, there was a significant negative correlation between the duration of SSSA subsequent to the stimulation session and the total number of intact pyramidal neurons observed in the bilateral CA1 and ipsilateral CA3 subfields of the status subgroup. There were significant differences between the status and non-status subgroups with respect to the number of afterdischarges (ADs) and the total AD duration during the stimulation session. Pretreatment with phenobarbital (30 mg/kg) prevented the development of SE and hippocampal cell loss completely. Pretreatment with MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist (0.25 or 1 mg/kg), also prevented hippocampal cell loss, although it did not block SE generation completely, which suggests dissociation of the mechanisms underlying the development of SE and hippocampal damage. These results indicate that prolonged SSSA actually causes hippocampal damage and it is critically dependent upon NMDA receptor participation.

Animals↗
PubMed1992

[Diffuse reduced uptake in 99m-Tc-HM-PAO SPECT and high level of neuron-specific enolase in cerebrospinal fluid in the early stage of Creutzfeldt-Jakob disease].

We report an autopsy-diagnosed case of Creutzfeldt-Jacob disease (CJD) showing diffuse reduced uptake in SPECT and a high level of neuron-specific enolase (NSE) in the cerebrospinal fluid (CSF). A 75-year-old woman with a 3-month history of progressive gait ataxia and dementia was examined. Four months after onset of the disease, she developed an akinetic mutism with normal CT and MRI. She was admitted for further examination, and electroencephalography showed periodic synchronous discharges. NSE in the CSF showed a high level at 90.6 ng/ml, and SPECT showed diffuse reduced uptake in the supratentorial region, with relatively spared uptake in the cerebellum. She died 13 months after onset of the disease, and the autopsy diagnosis was CJD. SPECT data and the level of NSE in CSF seem to be useful for clinical diagnosis and pathogenetic analysis in the early stage of CJD.

Aged↗
PubMed1991

Co-administration of either a selective D1 or D2 dopamine antagonist with methamphetamine prevents methamphetamine-induced behavioral sensitization and neurochemical change, studied by in vivo intracerebral dialysis.

Repeated administration of amphetamine or methamphetamine (MAP) causes behavioral sensitization in animals. Recently, several studies have revealed that in vivo release of dopamine from presynaptic nerve terminals of mesotelencephalic dopamine neurons is enhanced when sensitized animals are rechallenged with a psychostimulant. The present study investigated the effect of co-administration of SCH 23390 (a selective D1 dopamine receptor antagonist) or YM-09151-2 (a selective D2 dopamine receptor antagonist) prior to each MAP injection for 14 days on dopamine efflux in the striatal perfusates using in vivo dialysis. After 3 months drug abstinence, MAP challenge alone produced augmented stereotypy in the MAP group, but not in the control, the SCH 23390 + MAP or the YM-09151-2 + MAP group. In parallel with this behavioral observation, the degree to which dopamine efflux increased following the MAP challenge was significantly greater in the MAP group than that in the control, SCH 23390 + MAP group and the YM-09151-2 + MAP groups. While dopamine efflux after MAP challenge did not differ between the control and the YM-09151-2 + MAP group, it was greater in the SCH 23390 + MAP group than the control group. These results indicate that both D1 and D2 dopamine receptors play a role in the formation of behavioral sensitization, but with different mechanisms.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1991

Long-lasting change in the membrane-associated protein kinase C activity in the hippocampal kindled rat.

The effect of hippocampal kindling on protein kinase C (PKC) activity and protein concentration was investigated in rat amygdala/pyriform cortex (AM/PC) and right (contralateral) and left (ipsilateral) hippocampus (HIPP). There was no difference in cytosolic PKC activity between control and kindled groups in any part of the brain. The membrane-associated PKC activity was altered as follows. One week after the last seizure, it was significantly increased in both right (by 26%, P less than 0.05) and left HIPP (by 30%, P less than 0.02). Four weeks after the last seizure, it was significantly increased in the AM/PC (by 14%, P less than 0.02), right HIPP (by 37%, P less than 0.01) and left HIPP (by 24%, P less than 0.05). The protein concentrations in the crude cytosolic extracts prior to elution of PKC through DE-52 columns were significantly increased in the AM/PC (by 11%, P less than 0.05) and right HIPP (by 18%, P less than 0.02) 4 weeks after the last seizure. In the membrane extracts, there was a significant increase by 23% (P less than 0.02) in the left HIPP 1 week after the last seizure. In the fraction co-eluted with PKC, a significant increase in protein concentration of the cytosolic preparation was confirmed in the AM/PC (by 12%, P less than 0.05) as well as in the left HIPP (by 15%, P less than 0.05) 4 and 1 weeks respectively after the last seizure.(ABSTRACT TRUNCATED AT 250 WORDS)

Amygdala↗
PubMed1991

Lasting increase in D1 dopamine receptors in the lateral part of the substantia nigra pars reticulata after subchronic methamphetamine administration.

To examine the possible involvement of D1 dopamine receptors in behavioral sensitization induced by subchronic methamphetamine (MAP) administration, regional D1 receptors labeled with [3H]SCH 23390 were examined using binding assay and quantitative autoradiography. Rats received 4 mg/kg/day MAP (i.p.) for 14 days, and were decapitated after an abstinence period of 24 h, 7 days or 21 days. In MAP-treated rats, a significant decrease in Kd in the mesolimbic area was observed 24 h but not 7 days after the last injection. Neither Kd nor Bmax changed in the striatum or medial prefrontal cortex of MAP-treated rats after any period of abstinence. Autoradiography revealed a significant increase in specific [3H]SCH 22390 binding in the lateral part of the substantia nigra pars reticulata (SNr) of MAP-treated rats. Since this increase lasted up to 21 days after cessation of subchronic MAP administration, it is suggested that lasting increase in the nigral D1 receptors may be associated with the biological changes underlying MAP-induced behavioral sensitization.

Animals↗
PubMed1991

[Effectiveness of zotepine in therapy-refractory psychoses. An open, multicenter study in eight psychiatric clinics].

Zotepine was administered to 45 patients suffering from therapy-resistant psychoses hospitalized in eight psychiatric institutes (University Hospital Okayama and affiliated institutions). The psychoses of these patients were characterised by positive symptoms--predominantly hallucinations and delusions--and could not be influenced by a large variety of conventional antipsychotics, such as haloperidol. Previous medications were discontinued or administered together with zotepine. To assess changes in the pattern of symptoms, the Brief Psychiatric Rating Scale (BPRS) was employed over a period of up to 12 weeks at 2-week intervals. Ten patients dropped out of the study because of undesirable effects or for other reasons. 35 patients completed the 12-week study according to schedule. There was a relation between general improvement and certain patient characteristics. Zotepine proved to be effective especially in the catatonic type of schizophrenia, in chronic schizophrenias with acute exacerbation (DSM-III) and in relatively young patients in whom the disease had existed for a short time only. In the 26 patients who were markedly, moderately or slightly improved, BPRS score had dropped significantly after only two weeks of treatment. This points to a rapid onset of the therapeutic action of zotepine.

Adolescent↗