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Biomedical subjects

N Koshikawa

Publications and source records attributed to N Koshikawa.

At least 127 records · Page 7Linked to original sources
PubMed1989

Effects of SCH23390 injection into the dorsal striatum and nucleus accumbens on methamphetamine-induced gnawing and hyperlocomotion in rats.

The effects of SCH23390, a selective D1 receptor antagonist, injected into either the dorsal striatum or nucleus accumbens on methamphetamine-induced stereotyped gnawing and hyperlocomotion in rats were investigated. SCH23390 injected into the dorsal striatum did not alter the gnawing induced by both methamphetamine and apomorphine. However, SCH23390 injected into the nucleus accumbens significantly reduced methamphetamine-induced gnawing without altering the effects of apomorphine. Injection of SCH23390 into the nucleus accumbens reduced the hyperlocomotion produced by methamphetamine more markedly than injection of SCH23390 into the dorsal striatum.

Animals↗
PubMed1989

Antigenic variations of retrovirus in Japanese cancer patients.

Previously we demonstrated the prevalence of human T lymphotropic virus type I (HTVL-I) infection among cancer patients in Japan. This study was carried out to examine antigenic properties of retroviruses prevalent among Japanese cancer patients. Sera of 126 Japanese patients with cancer of different organs and with no history of blood transfusion, 94 in adult T cell leukemia (ATL)-endemic area and 32 in ATL-nonendemic area, were surveyed for antibodies to HTLV-I and HTLV-II by enzyme-linked immunosorbent assay (ELISA), Western blot analysis, and indirect immunogold electron microscopy. Among patients who were seropositive to HTLV-I, 39 of 56 (69.6%) in ATL-endemic area and 9 of 9 (100%) in ATL-nonendemic area were seropositive also to HTLV-II. Of 48 sera positive to both HTLV-I and HTLV-II, 34 (70.8%) showed stronger reactivities to HTLV-I than to HTLV-II. Among patients who were seronegative to HTLV-I, 3 of 38 (7.9%) in ATL-endemic area and 5 of 23 (21.7%) in ATL-nonendemic area were seropositive to HTLV-II. Antibodies appearing and disappearing in sera of patients examined during the clinical course reacted with peptide species of HTLV-I and/or HTLV-II not always consistent with peptide species cross-reactive between HTLV-I and HTLV-II. These results indicate the antigenic diversity of retroviruses prevalent among Japanese cancer patients.

Antigenic Variation↗
PubMed1988

Ketamine anaesthesia has no effect on striatal dopamine metabolism in rats.

Striatal levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid and homovanillic acid in rats were not altered for at least 6 h after a ketamine injection (100 mg/kg). Striatal DA turnover which was measured by giving alpha-methyl-p-tyrosine after ketamine was unchanged. Even the dose regimen of ketamine which anaesthetized animals for approximately 3.5 h (100 mg/kg + 5 maintenance injections of 50 mg/kg at 30 min intervals) produced no alteration in DA turnover for at least 9 h. These results suggest that ketamine anaesthesia will not adversely affect studies investigating central DAergic mechanisms in rats.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1988

Circadian studies of 5HT2 receptors: effects of clorgyline administration.

This paper demonstrates the application of an assay design that is particularly valuable for estimating receptor number (Bmax values) and affinity (Kd values) in many small samples of tissue. It is illustrated by its application to a study of possible circadian rhythms in the numbers of 5HT2 receptors in the rat cerebral cortex. The assay design involves the use of only two radioligand concentrations, the lower one being close to Kd (estimated from pilot studies) and the upper one close to 4 times this concentration. The results show that chronic clorgyline (1 mg/kg/day/28 days) administration to rats results in an 18% decrease in the number of cortical 5HT2 receptors (as measured by specific [3H]ketanserin binding). There is no significant circadian rhythm in receptor number in either the control or the MAOI-treated group. There is however, evidence of co-variation between the pairs of control animals housed in the same cage, and interestingly, that this effect is abolished by treatment with the MAOI.

Animals↗
PubMed1988

An examination of experimental design in relation to receptor binding assays.

1. Real and computer-simulated data were used to examine the efficiency of designs for receptor binding assays. 2. Initially, several different concentrations of [3H]-ketanserin were used in receptor binding studies, using membrane preparations from rat cerebral cortex to establish the form of the binding curves and to investigate the relationship between the variance of the binding measurements and their means. 3. The data showed that the specific binding could be modelled by a simple rectangular hyperbola, and were consistent with the assumption that the binding measurements have a constant coefficient of variation (0.1). 4. Computer-simulated data, with a coefficient of variation of 0.1, were then used to look at the precision of estimates of KD and Bmax obtained through the use of assay designs based on replicate incubations at two radioligand concentrations, or through the use of a geometric sequence of 5-7 radioligand concentrations. In each case, the influence of varying amounts (3.8-50%) of non-specific binding at KD on the precision of these estimates was monitored. 5. The results (a) illustrate the problems which arise in the analysis of receptor binding data when there are relatively high amounts of non-specific binding in combination with a constant coefficient of variation, (b) calculate the errors involved and (c) quantitate the relative merits of 2, 5, 6 and 7 point saturation curves in the estimation of Bmax and KD.

Animals↗
PubMed1987

Sulpiride injection into the dorsal striatum increases methamphetamine-induced gnawing in rats.

Sulpiride injected into the dorsal striatum enhanced both methamphetamine- and apomorphine-induced gnawing but blocked both when injected into the ventral striatum. The hyperlocomotion produced by methamphetamine was reduced by sulpiride injected into the dorsal striatum. The DA, DOPAC and HVA concentrations in the ventral striatum were increased 60 min after the injection of sulpiride into the dorsal striatum. Possible reasons for the enhancement of methamphetamine-induced gnawing by sulpiride injected into the dorsal striatum are discussed.

Animals↗
PubMed1987

Subcellular distribution of beta-adrenoceptors in brain following administration of antidepressant drugs.

The distribution of specific binding of [3H]dihydroalprenolol([3H]DHA) in sucrose gradients (0.2-1.75 M), containing homogenates of the cortex of rat brain, centrifuged to equilibrium (110,000 g/16 hr), was examined in controls and after treatment with antidepressant drugs. There were no significant changes in the specific binding of [3H]DHA after acute administration of desipramine (DMI, 50 mg/kg) or clorgyline (20 mg/kg), either in terms of the number of receptors or distribution in the sucrose gradient. There was a significant decrease (29%) in the number of beta-adrenoceptors after the chronic regimen with DMI, but again no apparent alteration in the density of the receptor-containing membranes, both samples having a maximum distribution at approximately 1.1 M sucrose. Non-specific binding was maximal at 0.65 M sucrose. Electron microscopy showed that the non-specific binding was largely to myelin and the fraction containing most specific binding was composed of membrane fragments. The activity of Na+ K+ ATPase had a single broad peak (maximum at 1.1 M sucrose). Thus, at the times studied, in vivo desensitisation/internalisation of cortical beta-adrenoceptors did not apparently occur following large acute doses of antidepressant drugs and furthermore the down-regulation which followed the chronic regimen with DMI did not involve migration of receptors into "light density fractions" which are reported to be present after acute exposure to agonists in vitro.

Animals↗
PubMed1987

Monitoring of dopamine metabolism by in vivo voltammetry and high performance liquid chromatography in L-dopa-treated rats.

Following L-DOPA administration, DA metabolites were measured by both in vivo voltammetry and HPLC-ECD. In vivo, the amplitudes of the catechol oxidation currents in both the striatum and frontal cortex increased and reached a plateau from 60 min to 240 min after L-DOPA treatment. L-DOPA, DA, DOPAC and HVA levels measured by HPLC-ECD after L-DOPA treatment were increased in both regions, and the occurrence of the peak of each compound was dependent on its order in the metabolic pathway, i.e., 15 min for DA, 45 min for DOPAC and 60-180 min for HVA. However, NE remained unchanged. No indication of a rapid DA increase was apparent in the catechol oxidation current at 15 min; and thus, DA is unlikely to be a main contributor to the catechol oxidation current in the brain of rats treated with L-DOPA.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Effects of antidepressant drug combinations on cortical 5-HT2 receptors and wet-dog shakes in rats.

Rats pretreated with the monoamine oxidase inhibitor, phenelzine 18 h (46.8 mg/kg) and 90 min (11.7 mg/kg) previously or only 90 min (46.8 mg/kg) previously developed a 5-HT dependent syndrome (including wet-dog shakes, WDS) when given the 5-HT uptake inhibitor, paroxetine (11.6 mg/kg). After 2 h, but only in rats pretreated with 2 injections of phenelzine, there was a gradual reduction in the number of cortical 5-HT2 receptors, determined in vitro with [3H]ketanserin, and this was temporally related to a reduction in the frequency of WDS. Both effects (down-regulation and WDS) were prevented by the 5-HT2 receptor antagonist, pirenperone. A second injection of paroxetine at 3 h evoked additional WDS in rats pretreated with 1 injection of phenelzine but not in rats pretreated with 2 injections, suggesting that spinal 5-HT2 receptors might also have been down-regulated at the same time. Similar results were obtained when rats were pretreated instead with the selective MAO A inhibitor, clorgyline or when given either citalopram or fenfluramine instead of paroxetine. 5-HTP also evoked WDS in phenelzine-treated rats and markedly increased brain 5-HT concentration but only slowly down-regulated 5-HT2 receptors; in carbidopa-treated animals, 5-HTP was without effect on receptor numbers despite production of frequent WDS. It thus appears that drugs which increase synaptic 5-HT (as indicated by production of WDS) by interference with the release or reuptake of 5-HT more readily down-regulate 5-HT2 receptors than 5-HTP which does not directly affect these mechanisms.

5-Hydroxytryptophan↗
PubMed1985

Is waning of a 5-hydroxytryptamine (5-HT)-mediated syndrome due to 5-HT2 receptor down-regulation?

The 5-hydroxytryptamine (5-HT) uptake inhibitor, paroxetine (11.6 mg/kg i.p.), given to rats pretreated with the monoamine oxidase inhibitor, phenelzine, 18 h (46.8 mg/kg i.p.) and 90 min (11.7 mg/kg i.p.) before, evoked a 5-HT-dependent syndrome which included wet-dog shakes (WDS). The frequency of WDS declined over the ensuing 3 h, at which time cortical 5-HT2 receptors showed a significant (30%) decrease in number. A second injection of paroxetine given at this time did not evoke a significant increase in the number of WDS, suggesting that spinal 5HT2 receptors might also have been down-regulated at the same time.

Animals↗
PubMed1982

["Methamphetamine-stereotypy and hypermotility" in rats chronically treated with reserpine--the effect of intracerebral injection of chlorpromazine].

In rats given methamphetamine (MAPT, 10 mg/kg i.p.) 24 hrs--48 hrs after the long term-administration of reserpine (RE), we have previously found such "bizarre-biting behaviour" as persistent and bloody biting activity at their own legs and tails or those of their cage mates. The present investigation examined the effect of a blockade of the dopamine receptor in the brain on MAPT-induced "bizarre-biting behaviour" and hypermotility of RE-pretreated rats. Male albino Wistar rats aged 4 weeks were injected intraperitoneally with RE (1.25 mg/kg) or 0.9% saline solution (1.25 ml/kg) every two days for 13 days. Twenty-three hrs after the last injection, rats received chlorpromazine (CP, 150 micrograms, 250 micrograms, 625 micrograms, or 1 mg/rat) intracerebrally by Valzelli's method; and 1 hr later, MAPT (10 mg/kg i.p.) was injected. MAPT-induced hypermotility was potentiated in the RE-pretreated rats, but it was suppressed dose-dependently by CP. Stereotyped licking and biting activities of saline-pretreated rats were completely suppressed by CP at each dose given, however, the "bizarre-biting behaviour" of RE-pretreated rats was inhibited by CP only at high doses (625 micrograms or 1 mg/rat). It is suggested that the MAPT-induced hypermotility of RE-pretreated rats is mediated by activation of dopamine receptor while their "bizarre-biting behaviour" is partially related to it.

Animals↗
PubMed1977

["Methamphetamine-stereotypies" and brain dopamine levels of rats treated with single or repeated doses of alpha-methyl-para-tyrosine (author's transl)].

Male albino Wistar rats were injected intraperitoneally with saline solution (1.0 ml/kg) or a-methyl-paratyrosine (50 mg/kg) once or daily X 7 and methamphetamine (10 mg/kg) was injected 3 hr or 24 hr after the last injection of these drugs. Stereotyped licking and biting activity were scored during 120 min after methamphetamine injection and, in parallel brain dopamine levels were measured. Methamphetamine given 3 hr after single or repeated administrations of alpha-methyl-para-tyrosine was not effective for stereotyped behavior and brain dopamine levels in similarly treated rats decreased markedly in comparison with saline-treated rats. Methamphetamine 24 hr after repeated administration of alpha-methyl-para-tyrosine clearly induced stereotypies and brain dopamine levels in these rats did not differ from saline-treated rats. The results suggest a possible role of brain dopamine on "methamphetamine-stereotypies".

Animals↗