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I Kusumi

Publications and source records attributed to I Kusumi.

At least 19 recordsLinked to original sources
PubMed2001

Effects of lithium on dopamine D2 receptor expression in the rat brain striatum.

Effects of lithium on the dopamine D2 receptor expression in the rat brain striatum were studied. Feeding the chow containing 0.2% LiCO3 for 6 days increased the level of the dopamine D2 receptor mRNA, and the transcription rate of the dopamine D2 receptor gene, indicating the stimulatory effects of lithium on the transcription of the dopamine D2 receptor gene. [3H] Spiperone binding to the striatal membranes increased in the rats treated with lithium, while the Western blotting analysis showed no change of the amount of the dopamine D2 receptors. These results suggested that lithium might induce the conformational changes of the dopamine D2 receptors. The methamphetamine-induced locomotor activity was enhanced by the pretreatment with lithium, whereas simultaneous increase in the methamphetamine concentration in the striatum was also observed. These observations suggested that the stimulation of methamphetamine-induced locomotor activity by lithium might be, at least partly, due to either increased sensitivity of the dopamine receptors, or increased concentration of methamphetamine in brain, or combination of both.

Animals↗
PubMed2001

Serotonin-induced platelet intracellular calcium mobilization in various psychiatric disorders: is it specific to bipolar disorder?

BACKGROUND: Serotonin (5-HT)-stimulated platelet intracellular calcium (Ca) mobilization has been reported to be enhanced in unmedicated depressive patients compared to those of normal healthy subjects, which suggests increased 5-HT2A receptor function in these patients. It has not been ascertained whether this enhanced response is specific to some type of affective disorders among various mental disorders. METHODS: We examined 5-HT-induced platelet intracellular Ca response in 152 unmedicated outpatients with various psychiatric disorders including bipolar disorder (BD), major depressive disorder with melancholia (DM), major depressive disorder without melancholia (DN), schizophrenia (SCH), panic disorder (PD), obsessive-compulsive disorder (OCD), social phobia (SP) and bulimia nervosa (BN), and 30 normal controls. RESULTS: We observed no significant differences in basal intracellular Ca concentration among all patient subgroups and normal controls. While the 5-HT-induced Ca response was significantly and specifically higher in patients with BD than in normal controls, no significant differences were found in the Ca response to 5-HT between patients with DM, DN, SCH, PD, OCD, SP and BN, and normal controls. LIMITATIONS: The sample sizes of each group are still small. Therefore, they have to be enlarged in the continuation of the study so as to increase the power of the statistical tests. CONCLUSION: These results indicate the possibility that enhanced signal transduction, mediated by the 5-HT2A receptor, may be specific to bipolar disorder.

Adult↗
PubMed2001

Nucleotide sequence analysis of the binding site on the inositol 1,4,5-trisphosphate type-1 receptor in bipolar disorder -- a negative study.

Pharmacological studies of bipolar disorder suggest that dysfunction of calcium mobilization via phosphatidylinositol-mediated transduction may be involved in its pathogenesis. The present study tests the hypothesis that dysfunction of calcium mobilization in bipolar disorder is due to the mutation of the nucleotide sequence in the FKBP12 binding site on the inositol 1,4,5-trisphosphate type-1 receptor (IP(3)R1). Nucleotide sequence analysis of the FKBP12 binding site on IP(3)R1 was performed using reverse transcription-polymerase chain reaction and DNA sequencing. The nucleotide sequence in this region was preserved in all subjects. This finding suggests that IP(3)R1 dysfunction through the FKBP12 binding site is not involved in the pathogenesis of bipolar disorder.

Adult↗
PubMed2001

Effects of acute citalopram treatment on the methamphetamine-induced locomotor activity.

1. Previously the authors have shown that acute citalopram treatment increased the dopamine D2 receptor expression in rat brain striatum (Kameda et al., 2000). In the present study, the authors attempted to determine whether these effects of citalopram influence the methamphetamine-induced locomotor activity. 2. The pretreatment with a single administration of citalopram (10 mg/kg, i.p.) resulted in the significant enhancement of the locomoter activity induced by methamphetamine treatment (1 mg/kg, i.p.). The enhancement was observed 30 min, 12 hours, 24 hours, but not 7 days after withdrawal of citalopram administration. 3. Then the authors determined the methamphetamine concentration in rat brain striatum by gas chromatography-mass spectrometry (GC-MS) The results showed that the concentration of methamphetamine wars significantly higher in the rats 24 hours, and also 7 days after withdrawal of citalopram administration, compared to the control rats. 4. These results emphasized the involvement of the high methamphetamine concentration, caused by the pretreatment with citalopram, in the enhancement of the methamphetamine-induced locomotor activity. However high methamphetamine concentration alone could not account for this enhancement, since the high concentration of methamphetamine observed 7 days after withdrawal of citalopram administration did not appear to enhance the methamphetamine-induced locomotor activity. Another mechanism through which the pretreatment with citalopram enhanced the methamphetamine-induced locomotor activity, such as the increased expression of the dopamine D2 receptors, could not be excluded.

Animals↗
PubMed2000

Differential effects of subchronic treatments with atypical antipsychotic drugs on dopamine D2 and serotonin 5-HT2A receptors in the rat brain.

The effects of 3-week treatment with a typical antipsychotic drug chlorpromazine and three atypical antipsychotic drugs (risperidone, olanzapine and perospirone) on the binding to dopamine D2 and serotonin 5-HT2A receptors were examined in the rat stratum and frontal cortex, respectively. Subchronic treatment with chlorpromazine (10 mg/kg) and perospirone (1 mg/kg) significantly increased D2 receptors, while no increase was observed with lower dose of chlorpromazine (5 mg/kg), perospirone (0.1 mg/kg), risperidone (0.25, 0.5 mg/kg) or olanzapine (1, 2 mg/kg). On the other hand, 3-week administration of chlorpromazine (5, 10 mg/kg) and olanzapine (1, 2 mg/kg) significantly decreased 5-HT2A receptors, but risperidone (0.25, 0.5 mg/kg) or perospirone (0.1, 1 mg/kg) had no effect. The measurement of in vivo drug occupation for D2 and 5-HT2A receptors using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) suggested that high occupation of 5-HT2A receptors with lower D2 receptor occupancy might be involved in the absence of up-regulation of D2 receptors after subchronic treatment with some atypical antipsychotic drugs.

Animals↗
PubMed2000

Open pergolide treatment of tricyclic and heterocyclic antidepressant-resistant depression.

BACKGROUND: Recently, a dopamine hypothesis of depression was put forward, and several studies have demonstrated that direct and indirect dopamine agonists have antidepressant effects. METHODS: Using Clinical Global Impressions, we evaluated the efficacy of 4-week treatment of pergolide as an antidepressant adjuvant involving 20 unipolar depressed patients who were refractory to standard treatment with antidepressants. RESULTS: One patients (5%) were very much improved, seven (35%) much improved, four (20%) minimally improved, six (30%) no change or worse, and two (10%) not assessed. There was no significant difference in any clinical factors between the pergolide responder and non-responder group. LIMITATIONS: This study was a non-blind open trial, and pergolide was added to tricyclic and heterocyclic antidepressants. CONCLUSION: Pergolide may be useful as an antidepressant adjuvant, suggesting a potential role for dopamine-2 stimulation in the antidepressant response.

Adult↗
PubMed2000

Treatment response in depressed patients with enhanced Ca mobilization stimulated by serotonin.

Serotonin (5-HT)-stimulated intraplatelet calcium (Ca) mobilization has been shown to be enhanced in nonmedicated depressive patients by many studies. However, there has not been any longitudinal follow-up study of this parameter. We examined the relationship between treatment response and pretreatment value of the 5-HT-induced Ca response. The 5-HT(10 microM)-induced intraplatelet Ca mobilization was measured in 98 nonmedicated depressive patients (24 bipolar disorders, 51 melancholic major depressive disorders, and 23 non-melancholic major depressive disorders). These patients were followed up prospectively for a further period of five years. The depressed patients with enhanced Ca response to 5-HT in bipolar disorders exhibited a good response to mood stabilizers but those with major depressive disorders showed a poor response to antidepressants. These findings suggest the possibility that the 5-HT-induced intraplatelet Ca response may be a good predictor of treatment response in depressed patients. Longer longitudinal follow-up studies are needed in larger samples to examine if this parameter may be a specific biological marker for unipolar-bipolar dichotomy.

Adult↗
PubMed2000

Human leukocyte antigen and season of birth in Japanese patients with schizophrenia.

OBJECTIVE: Five Japanese studies, to the authors' knowledge, without exception, have consistently shown an increased frequency of human leukocyte antigen (HLA)-DR1 in patients with schizophrenia. This suggests an association between HLA-DR1 and schizophrenia in the Japanese population. The mechanism of the association is unknown; however, prenatal infections may be involved. The present study explored factors, including winter birth, that might correlate with this mechanism. Age at onset and gender were also studied. METHOD: Factors were compared between Japanese patients with schizophrenia with and in those without HLA-DR1 (N=60 and N=307, respectively). RESULTS: A significantly higher incidence of births in February and March was observed in patients with (31.7%) than those without (15. 6%) HLA-DR1. No association was found between the presence of HLA-DR1 and other variables. CONCLUSIONS: Although this result is preliminary, it may suggest an interaction between HLA and winter birth in the development of schizophrenia in the Japanese population.

Adult↗
PubMed1999

Algorithms for the treatment of acute side effects induced by neuroleptics.

This article focuses especially on acute extrapyramidal symptoms (EPS) and neuroleptic malignant syndrome (NMS) induced by antipsychotic treatments. Strategies for the management of acute EPS may include changing the neuroleptic (NL) to an alternative one, i.e. switching to a low-potency or an atypical antipsychotic, lowering the dosage or discontinuing the NL, and adding a drug effective in treating EPS. The important factors in the management of NMS are early recognition, immediate discontinuation of antipsychotic medications and prompt institution of supportive care. Dantrolene and/or bromocriptine are found to be the most effective for the second-step treatment of NMS in Japan.

Algorithms↗
PubMed1998

In vivo occupation of dopamine D1, D2 and serotonin2A receptors by novel antipsychotic drug, SM-9018 and its metabolite, in rat brain.

In vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by a novel antipsychotic drug, SM-9018 (perospirone hydrochloride; cis-N- [4- [4- (1,2-benzisothiazol-3-yl)- 1-piperazinyl]butyl]cyclohexane-1,2-dicarboximide monohydrochloride) and its major metabolite (ID-15036; N-[4-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]butyl]-1-hydroxy-1 , 2-cyclohexanedicarboximide) was measured in rat brain using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist, at these receptor sites. SM-9018 and its metabolite, ID-15036, dose-dependently reversed EEDQ-induced 5-HT2A and D2 receptor inactivation, but not D1 receptor inactivation. At lower doses (0.1 mg/kg i.p.), SM-9018 showed a preferential occupation of the 5-HT2A receptors, with only a small effect on the D2 receptors; while at higher doses (1.0 and 5.0 mg/kg i.p.), it was nearly equipotent in its occupation of both the D2 (77.8%) and the 5-HT2A receptors (78.6%). On the other hand, ID-15036 was more potent in occupying the 5-HT2A than the D2 receptors even at higher doses (1.0 and 5.0 mg/kg i.p.). We previously reported that atypical antipsychotic drugs, such as clozapine, were characterized by a high occupancy of the 5-HT2A receptors, with a low or minimum occupancy of the D2 receptors in vivo. The present study suggests that SM-9018 and its metabolite ID-15036 show a preferential tendency to occupy 5-HT2A receptors, and that the clozapine-like atypical properties of SM-9018 may be due to some pharmacological action of both the SM-9018 itself and its metabolite, ID-15063.

Animals↗
PubMed1998

A serotonin-4 receptor-like pseudogene in humans.

During a search for new G-protein-linked receptors for dopamine and serotonin, we found a serotonin-4 receptor-like pseudogene. This receptor-like pseudogene is intronless, contains an in-frame stop codon following transmembrane-3, and has two one-nucleotide insertions between transmembrane-5 and -6 regions which alter the reading frame. The predicted amino acid sequence of the human pseudogene is about 35% identical with that of the rat serotonin-4 receptor.

Amino Acid Sequence↗
PubMed1998

A human serotonin-7 receptor pseudogene.

Although the serotonin-7 receptor was cloned several years ago, its localization in brain tissues remains confusing because of the existence of a related expressed pseudogene, the sequence of which has not hitherto been reported. During the course of searching for related receptor genes, we also searched for this pseudogene to determine its sequence. Human genomic DNA was screened for dopamine and serotonin receptor-like genes, using the polymerase chain reaction method and degenerate oligonucleotide primers based on the similar sequences in the transmembrane-6 and -7 regions of the serotonin-5A, the serotonin-7, and the dopamine D2, D3 and D4 receptors. This resulted in one of the clones having a 115 bp fragment, of which 89% of the bases were identical to the transmembrane-6 and -7 regions of the serotonin-7 receptor sequence. The fragment was radiolabelled and used to screen a human fetal brain cDNA library. A novel cDNA clone of 1326 bp was isolated. Based on the nucleotide sequence, 88% of the bases in this sequence of the pseudogene are identical to the human serotonin-7 receptor coding sequence. However, compared to the serotonin-7 receptor DNA sequence, the pseudogene sequence has nucleotide deletions and insertions, resulting in frame-shifts and stop codons. It was concluded that this sequence represented a pseudogene related to the serotonin-7 receptor gene.

Amino Acid Sequence↗
PubMed1998

In vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by sertindole in the rat brain.

OBJECTIVE: To determine the in vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by novel antipsychotic agent sertindole using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist at these receptor sites. DESIGN: Animal study. INTERVENTIONS: Intraperitoneal administration to Wistar rats of 1 of 4 test compounds: a control compound of 0.15% tartaric acid, or a compound of either sertindole (0.5 mg/kg or 2.0 mg/kg) or clozapine (20 mg/kg) dissolved in 0.15% tartaric acid 1 hour before intraperitoneal administration of EEDQ (8 mg/kg) or ethanol/water solution. RESULTS: Sertindole exhibited little or no effect on D1 and D2 binding sites in vivo. On the other hand, sertindole occupied 5-HT2A receptors more extensively and firmly than EEDQ. This study indicates that sertindole is characterized by high occupancy of 5-HT2A receptors and by low or minimum occupancy of D1 and D2 receptors. CONCLUSIONS: These characteristics are very similar to atypical antipsychotic agents such as clozapine. Sertindole's low liability to cause extrapyramidal side effects (EPS) may be related to greater long-term binding for 5-HT2A receptors relative to D2 receptors.

Animals↗
PubMed1998

The human serotonin-7 receptor pseudogene: variation and chromosome location.

We report a variation of the pseudogene for the serotonin-7 receptor in human DNA. Human genomic DNA was amplified, using the polymerase chain reaction method and degenerate oligonucleotide primers for serotonin receptor-like genes. A novel gene DNA sequence of 1325 bp was found. Based on nucleotides, this gene is 88% identical to the serotonin-7 receptor coding sequence. Compared with the previously known serotonin-7 receptor pseudogene, this pseudogene has 1 nucleotide deletion and 4 nucleotide mutations. The gene is located on human chromosome 12 at 12p12.3-p13.2.

Chromosomes↗
PubMed1997

Effects of serotonergic agents on the up-regulation of dopamine D2 receptors induced by haloperidol in rat striatum.

We examined the modulatory effect of serotonergic activities on haloperidol-induced up-regulation of dopamine D2 receptors in rat striatum. Chronic treatment with haloperidol (0.1, 0.5 mg/kg, i.p., 3 weeks) increased the number of dopamine D2 receptors, while no increase was observed with the atypical antipsychotic drugs clozapine (10 mg/kg) and trans-5-chloro-2-methyl-2,3,3a, 12b-tetrahydro-1 H-dibenz[2,3:6,7]oxepino[4,5-c]pyrrolidine maleate (ORG 5222; 0.25 mg/kg). Chronic treatment with 6-chloro-2-(1-piperazinyl)pyrazine (MK-212), a nonselective serotonin (5-hydroxytryptamine, 5-HT) receptor agonist (2.5 mg/kg), or with citalopram, a 5-HT reuptake inhibitor (10 mg/kg), potentiated the haloperidol (0.1 mg/kg)-induced up-regulation of dopamine D2 receptors, while that with (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a 5-HT1A receptor agonist (0.1 mg/kg) had no influence on the dopamine D2 receptor up-regulation. Coadministration of ritanserin (1 mg/kg), a 5-HT2A/2C receptor antagonist, with a low dose of haloperidol (0.1 mg/kg), but not with a high dose of the agent (0.5 mg/kg) attenuated the dopamine D2 receptor up-regulation, Drug occupation of 5-HT2A and dopamine D2 receptors in vivo examined using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) was 69.8% and 45.1%, respectively, after the acute administration of haloperidol (0.1 mg/kg) plus ritanserin (1 mg/kg). This profile, that 5-HT2A receptors are highly occupied compared with dopamine D2 receptors, was similar to that of clozapine or ORG 5222. These results suggest that potent 5-HT2A receptor antagonism versus weak dopamine D2 receptor blockade may be involved in the absence of up-regulation of dopamine D2 receptors after chronic treatment with clozapine or ORG 5222.

Animals↗
PubMed1995

Characterization of [3H]clozapine binding sites in rat brain.

We examined the characteristics of [3H]clozapine binding sites in four rat brain regions (frontal cortex, limbic area, hippocampus and striatum) in order to elucidate the pharmacological profile of this unique atypical antipsychotic drug. The specific [3H]clozapine binding was found to be saturable and reversible in all these brain regions. Scatchard analysis of the saturation data indicated that the specific binding consisted of high- and low-affinity components. Displacement experiments showed that the muscarinic cholinergic receptor represented about 50% of [3H]clozapine binding in each brain area. Serotonin 5-HT2 and dopamine D4 receptor binding sites could also be detected by displacement experiments using ketanserin and nemonapride, respectively, in frontal cortex and limbic area, but not in hippocampus or striatum. Alpha-1, alpha-2, histamine H1, dopamine D1, D2, or D3 receptor components could not be determined within the high-affinity [3H]clozapine binding sites in any brain region. It is possible that the atypical property of clozapine may depend on the modulatory effect on dopaminergic function via 5-HT2 receptor blockade and/or may be mediated via D4 receptor blockade in the mesocortical and mesolimbic area.

Animals↗
PubMed1995

Long-term treatment with haloperidol or clozapine does not affect dopamine D4 receptors in rat frontal cortex.

We examined the effects of long-term treatment with haloperidol and clozapine on dopamine D4 receptors in rat frontal cortex. Dopamine D4 receptor binding sites were indirectly determined from the displacement experiments of [3H]clozapine binding using nemonapride. Three-weeks administration of haloperidol (0.5 mg/kg) or clozapine (10 mg/kg) did not significantly affect the D4 receptors in the frontal cortex. The density of D2 receptors, determined by [3H]spiperone binding to striatum, was increased by long-term treatment with haloperidol, but it was not significantly changed by that with clozapine.

Animals↗