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Akitane Mori - One of the best experts on this subject based on the ideXlab platform.
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Effect of chronic Ceruletide treatment on dopaminergic neurotransmitters, receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile
Brain Research, 1993Co-Authors: Hiroshi Hirata, Masato Asanuma, Norio Ogawa, Zensuke Ota, Akitane MoriAbstract:Abstract To clarify the mechanism of long-lasting Ceruletide action, an analogue of cholecystokinin, in relieving the dyskinesia induced by the iminodipropionitrile (IDPN), we investigated the changes in dopaminergic neuronal system in the striatum. In the control rats, Ceruletide had no significant effect on the concentrations of dopamine (DA), DOPAC or HVA or on the turnover of DA in the striatum. The concentration of DA was decreased and the turnover of DA [(DOPAC + HVA)/DA] was increased in the striatum of IDPN-treated rats. Chronic administration of Ceruletide (160 μ g· kg −1 ·day −1 × 10days) increased DA concentration and decreased DA turnover only transiently Both. D 1 and D 2 receptors and their mRNAs were decreased in the striatum of rats given IDPN. After chronic Ceruletide treatment, D 1 receptor rose to the control level for 3 days, while the D 2 receptor rose to a level 1.5 times the control level for 3 days. Even at the 7 days after chronic Ceruletide treatment, D 2 -R rose significantly as compared with the IDPN-treated rats. Both D 1 and D 2 receptor mRNAs were significantly increased for 3 days in the IDPN-treated rats. These observations indicate that the synthesis of DA receptors is increased by Ceruletide treatment in the striatum of IDPN-treated rats. These changes in DA receptors and their mRNAs closely paralleled the changes in dyskinetic movement of the IDPN-treated rats after repeated daily administration of Ceruletide, as previously reported. The parallel changes between the DA receptors and dyskinetic movement suggest that an up-regulation of DA receptors in the striatum corresponds with an improvement of dyskinesia in the IDPN-treated rats. Thus, the efficacy of Ceruletide in treating the dyskinesia induced by IDPN may be related to the up-regulation of DA receptors in the striatum.
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Late onset and long-lasting suppressive effects of Ceruletide, an analogue of cholecystokinin, on c-fos mRNA expression in the rat striatum.
Neuroscience letters, 1992Co-Authors: Masato Asanuma, Norio Ogawa, Hiroshi Hirata, K. Haba, H. Chou, Akitane MoriAbstract:Abstract C- fos mRNA expression by stimulation with subcutaneous (s.c.) administration of saline or cycloheximide (CHX) was examined in the rat striatum with or without pretreatment with Ceruletide, an analogue of cholecystokinin. The c- fos mRNA induction 1 h after CHX stimulation (25 mg/kg, s.c.) was significantly suppressed by Ceruletide pretreatment (80 μg/kg, s.c.) 2 h before CHX stimulation in the striatum, and tended to be suppressed by Ceruletide pretreatment 4 h before saline or CHX stimulation. Long-lasting and inhibitory effects of Ceruletide on dyskinesia and on dopaminergic (DAergic) neuronal systems, and c- fos mRNA expression by activation of the DAergic system have been reported. The present findings together with previous reports suggest that Ceruletide might have late onset and long-lasting suppressive effects on the expression of c- fos mRNA in the striatum and that these effects might be related to its effects on DAergic neuronal transmission.
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Long-lasting effect of Ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile
Brain research, 1991Co-Authors: Norio Ogawa, Masato Asanuma, K. Haba, Akitane MoriAbstract:Abstract In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of Ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 μg/kg Ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of Ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by Ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with Ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of Ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals. The observed beneficial effect of Ceruletide on impaired neuronal pathways indicates that it acts as a ‘neuro-normalizer’ in the animal model of IDPN-induced dyskinesia.
Akira Matsushita - One of the best experts on this subject based on the ideXlab platform.
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Differential effects of Ceruletide on amphetamine-induced behaviors and regional dopamine release in the rat
European journal of pharmacology, 1993Co-Authors: Tsuyoshi Kihara, Masato Ikeda, Katsuaki Matsubara, Akira MatsushitaAbstract:Abstract This study concerned the effects of Ceruletide, a cholecystokinin (CCK)-related peptide, on amphetamine-stimulated behaviors (hyperlocomotion and stereotypy) and amphetamine-induced dopamine (DA) release from the striatum and the nucleus accumbens of the rat. Also, behavioral alterations due to Ceruletide administration were compared with the change in DA release from these areas. Ceruletide 160 μg/kg s.c., attenuated hyperlocomotion induced by amphetamine, 1 mg/kg and 3 mg/kg s.c., but had no effect on amphetamine-induced stereotypy. Results from in vivo microdialysis experiments showed that s.c. administration of Ceruletide caused a significant inhibition of the amphetamine-induced increase in DA release in the nucleus accumbens but not in the striatum. These neurochemical inhibitory effects of Ceruletide dissappeared completely with bilateral subdiaphragmatic vagotomy. However, infusion of 1 μM of Ceruletide into the nucleus accumbens through the dialysis probe had no effect on amphetamine-induced DA release. These results suggest that the inhibitory effect of peripheral administration of Ceruletide on amphetamine-induced hyperlocomotion is closely related to the change in DA release from the nucleus accumbens. In the nucleus accumbens, systematically administered Ceruletide acts initially on the peripheral organs and influences the activity of DA terminals via an unknown path related to the vagus. Ceruletide had different actions on the dopaminergic system in the striatum and that in the nucleus accumbens.
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Influence of potassium concentration in microdialysis perfusate on basal and stimulated striatal dopamine release: effect of Ceruletide, a cholecystokinin-related peptide.
Journal of neurochemistry, 1993Co-Authors: Tsuyoshi Kihara, Masato Ikeda, Hiroshi Miyazaki, Akira MatsushitaAbstract:The in vivo microdialysis method was used to study the effect of the cholecystokinin-related peptide, Ceruletide, on extracellular levels of dopamine (DA) in the striatum following perfusion with various K+ concentrations. Increasing the K+ concentration in the perfusate from 4 to 15 or 17.5 mM did not change basal DA release or release evoked by electrical stimulation of the medial forebrain bundle (MFB). However, when the perfusing solution contained 20 or 30 mM K+, dose-dependent reductions of both basal and MFB-stimulated DA release occurred. Subcutaneous administration of Ceruletide at 160 micrograms/kg had no influence on the basal or MFB-stimulated DA release with 4 or 15 mM K+ in the perfusate. However, after perfusion with 17.5 mM K+, Ceruletide significantly attenuated the basal and MFB-stimulated DA release. Carbachol (10 microM) locally applied via the dialysis probe also attenuated MFB-stimulated DA release after perfusion with 17.5 mM K+. From these results, we conclude that under appropriate depolarization of striatal DA terminals, Ceruletide induces further depolarization and inactivation of nigrostriatal DA terminals. The present data suggest that this effect may be mediated via intrinsic cholinergic neurons in the striatum.
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inhibitory effect of cck 8 and Ceruletide on glutamate induced rises in intracellular free calcium concentrations in rat neuron cultures
Brain Research, 1992Co-Authors: Shunji Shinohara, Masami Eigyo, Goro Katsuura, Haruyuki Shintaku, Nobuhiro Ibii, Akira MatsushitaAbstract:To study the mechanism by which cholecystokinin octapeptide (CCK-8) and its potent analogue, Ceruletide, prevent glutamate-induced neuronal cell death in rat neuron cultures, we examined the effect of both peptides on glutamate-induced increases in the intracellular free calcium concentrations ([Ca2+]i), which are known to be a crucial trigger of the neurodegeneration induced by glutamate. CCK-8 itself did not alter [Ca2+]i in rat neuron cultures. Glutamate increased [Ca2+]i in neuron cultures rapidly and markedly. CCK-8 and Ceruletide significantly suppressed the increases in [Ca2+]i induced by glutamate. The maximum inhibitory effects of CCK-8 and Ceruletide at 10(-6) M reached 43 and 46% of the response to glutamate, respectively. Gastrin-I and CCK-4 also significantly attenuated the increases in [Ca2+]i induced by glutamate. The inhibitory effect of CCK-8 was completely blocked by the selective antagonist for CCK-B receptors, (+)L-365,260, but not by (-)L-364,718, which is a selective antagonist for CCK-A receptors. CCK-8 significantly suppressed [Ca2+]i response to kainate and high concentrations of extracellular K+, but not to N-methyl-D-aspartate. With cultured astrocytes, CCK-8 did not inhibit the increment of [Ca2+]i induced by glutamate. These findings clearly demonstrated that CCK-8 and Ceruletide inhibit glutamate-induced increases in [Ca2+]i in neuron cultures through CCK-B receptors, suggesting that CCK-8 may participate in the central actions of glutamate.
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Systemic administration of a cholecystokinin analogue, Ceruletide, protects against ischemia-induced neurodegeneration in gerbils
European journal of pharmacology, 1992Co-Authors: Masami Eigyo, Goro Katsuura, Haruyuki Shintaku, Shunji Shinohara, Akira Katoh, Teruo Shiomi, Akira MatsushitaAbstract:Abstract The neuroprotective action of a cholecystokinin octapeptide analogue, Ceruletide, was evaluated in models of cerebral ischemia using Mongolian gerbils. Ceruletide significantly suppressed the hyperactivity and amnesia induced by ischemia when injected s.c. 30 min before 5-min occlusion of the bilateral common carotid arteries at room temperature or immediately after their reperfusion. Ceruletide also reduced behavioral changes in ischemic gerbils whose body temperature was maintained at 37°C during the 3-min occlusion. In these groups, delayed neuronal cell death in the hippocampal CA1 area following ischemia was markedly attenuated by s.c. administration of Ceruletide. On the other hand, Ceruletide could not inhibit the behavioral changes or the neurodegeneration induced in the hippocampal CA1 area by 5-min occlusion at 37°C. These findings indicate that peripheral injection of Ceruletide produces a neuroprotective action against moderate cerebral ischemia, which is the first evidence suggesting the efficacy of Ceruletide in neurodegenerative diseases.
Norio Ogawa - One of the best experts on this subject based on the ideXlab platform.
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Effect of chronic Ceruletide treatment on dopaminergic neurotransmitters, receptors and their mRNAs in the striatum of rats with dyskinesia induced by iminodipropionitrile
Brain Research, 1993Co-Authors: Hiroshi Hirata, Masato Asanuma, Norio Ogawa, Zensuke Ota, Akitane MoriAbstract:Abstract To clarify the mechanism of long-lasting Ceruletide action, an analogue of cholecystokinin, in relieving the dyskinesia induced by the iminodipropionitrile (IDPN), we investigated the changes in dopaminergic neuronal system in the striatum. In the control rats, Ceruletide had no significant effect on the concentrations of dopamine (DA), DOPAC or HVA or on the turnover of DA in the striatum. The concentration of DA was decreased and the turnover of DA [(DOPAC + HVA)/DA] was increased in the striatum of IDPN-treated rats. Chronic administration of Ceruletide (160 μ g· kg −1 ·day −1 × 10days) increased DA concentration and decreased DA turnover only transiently Both. D 1 and D 2 receptors and their mRNAs were decreased in the striatum of rats given IDPN. After chronic Ceruletide treatment, D 1 receptor rose to the control level for 3 days, while the D 2 receptor rose to a level 1.5 times the control level for 3 days. Even at the 7 days after chronic Ceruletide treatment, D 2 -R rose significantly as compared with the IDPN-treated rats. Both D 1 and D 2 receptor mRNAs were significantly increased for 3 days in the IDPN-treated rats. These observations indicate that the synthesis of DA receptors is increased by Ceruletide treatment in the striatum of IDPN-treated rats. These changes in DA receptors and their mRNAs closely paralleled the changes in dyskinetic movement of the IDPN-treated rats after repeated daily administration of Ceruletide, as previously reported. The parallel changes between the DA receptors and dyskinetic movement suggest that an up-regulation of DA receptors in the striatum corresponds with an improvement of dyskinesia in the IDPN-treated rats. Thus, the efficacy of Ceruletide in treating the dyskinesia induced by IDPN may be related to the up-regulation of DA receptors in the striatum.
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Late onset and long-lasting suppressive effects of Ceruletide, an analogue of cholecystokinin, on c-fos mRNA expression in the rat striatum.
Neuroscience letters, 1992Co-Authors: Masato Asanuma, Norio Ogawa, Hiroshi Hirata, K. Haba, H. Chou, Akitane MoriAbstract:Abstract C- fos mRNA expression by stimulation with subcutaneous (s.c.) administration of saline or cycloheximide (CHX) was examined in the rat striatum with or without pretreatment with Ceruletide, an analogue of cholecystokinin. The c- fos mRNA induction 1 h after CHX stimulation (25 mg/kg, s.c.) was significantly suppressed by Ceruletide pretreatment (80 μg/kg, s.c.) 2 h before CHX stimulation in the striatum, and tended to be suppressed by Ceruletide pretreatment 4 h before saline or CHX stimulation. Long-lasting and inhibitory effects of Ceruletide on dyskinesia and on dopaminergic (DAergic) neuronal systems, and c- fos mRNA expression by activation of the DAergic system have been reported. The present findings together with previous reports suggest that Ceruletide might have late onset and long-lasting suppressive effects on the expression of c- fos mRNA in the striatum and that these effects might be related to its effects on DAergic neuronal transmission.
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Long-lasting effect of Ceruletide on dyskinesia and monoaminergic neuronal pathways in rats treated with iminodipropionitrile
Brain research, 1991Co-Authors: Norio Ogawa, Masato Asanuma, K. Haba, Akitane MoriAbstract:Abstract In a model of dyskinesia induced by the administration of iminodipropionitrile (IDPN) in the rat, we evaluated the effects of Ceruletide, an analogue of cholecystokinin, on behavioral abnormalities and monoaminergic neuronal function. Vertical head twitching in the IDPN-treated animals was inhibited for over 5 h following a single subcutaneous dose of 160 μg/kg Ceruletide. In animals dosed daily for 2 or 3 days, the number of head twitches at 24 h after the last dose was about one-third of the number before treatment. After repeated daily doses of Ceruletide for 6 days, the number of head twitches was reduced to low levels and remained significantly below pretreatment levels until the 4th posttreatment day. These results indicate that the inhibition of dyskinesia by Ceruletide was long-lasting. Assays of monoaminergic neurotransmitters and their metabolites in various brain regions indicate that an imbalance between dopaminergic and serotonergic neuronal systems plays a major role in the pathogenesis of the IDPN-induced dyskinesia, i.e. the ratio of (DOPAC+HVA)/5-HIAA was significantly greater in the striatum but significantly smaller in the hippocampus of the IDPN-treated vs normal animals. This initially abnormal ratio of (DOPAC+HVA)/5-HIAA in the striatum and hippocampus of IDPN-treated animals returned to normal following treatment with Ceruletide, corresponding with the reduction of the head twitching. The alterations in monoaminergic neuronal function induced by repeated administration of Ceruletide persisted for at least 3 days, even though its plasma half-life is several minutes. Ceruletide also exerted a marked effect on monoaminergic neuronal function in the IDPN-treated rats, in contrast to only a slight effect in normal animals. The observed beneficial effect of Ceruletide on impaired neuronal pathways indicates that it acts as a ‘neuro-normalizer’ in the animal model of IDPN-induced dyskinesia.
Gohei Yagi - One of the best experts on this subject based on the ideXlab platform.
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Treatment of tardive dyskinesia with Ceruletide: a double-blind, placebo-controlled study.
Psychiatry research, 1992Co-Authors: Takuya Kojima, Toshio Yamauchi, Matsue Miyasaka, Yoshifumi Koshino, Yoshibumi Nakane, Ryo Takahashi, Yasuo Shimazono, Gohei YagiAbstract:Abstract The effectiveness of a once-weekly i.m. injection of Ceruletide (0.8 μg/kg) in suppressing the symptoms of neuroleptic-induced tardive dyskinesia (TD) was evaluated in a double-blind, placebo-controlled, matched-pairs study. Global evaluation of the severity of TD symptoms over the 8-week study period revealed a significant improvement with Ceruletide as compared with placebo. Analysis of the therapeutic response to Ceruletide over the course of treatment revealed a slow, but long-lasting improvement of TD symptoms. Side effects, which were mild and transient, consisted mainly of nausea and epigastric discomfort. The incidence of side effects did not differ between the Ceruletide-and placebo-treated groups. Ceruletide appears to be a novel and practical treatment that can substantially alleviate the symptoms of dyskinesia.
Hisashi Kuribara - One of the best experts on this subject based on the ideXlab platform.
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Ceruletide a cholecystokinin like decapeptide differentially reduces the stimulant effect of mk 801 and ketamine evaluation by discrete shuttle avoidance in mice
European Journal of Pharmacology, 1993Co-Authors: Hisashi KuribaraAbstract:Abstract The non-competitive NMDA antagonist, MK-801 (dizocilpine: 0.03–0.3 mg/kg i.p.), a dissociative anesthetic, ketamine (1–20 mg/kg s.c.) and a CNS stimulant, methamphetamine (0.1–1 mg/kg s.c.), dose dependently increased the response rate in mice trained to discrete shuttle avoidance. MK-801 (0.1 mg/kg), ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg) were almost equipotent. The cholecystokinin-like decapeptide, Ceruletide, 0.1 μg/kg s.c., completely attenuated the response-increasing effect of MK-801 (0.1 mg/kg), although at this dose Ceruletide alone did not produce any significant change in the avoidance response. Up to 10 μg/kg of Ceruletide, which itself decreased the response rate, was required to reduce significantly the response-increasing effect of ketamine (10 mg/kg) and methamphetamine (0.3 mg/kg). On the other hand, haloperidol (0.01–0.1 mg/kg s.c.) decreased both the response rate and the % avoidance dose dependently, and inhibited the response-increasing effects of MK-801, ketamine and methamphetamine to almost the same degree. The present results suggest that comparatively lower doses of Ceruletide inhibit selectively the stimulant effect of MK-801. Inhibition of dopamine release from the stored site in the nucleus accumbens may be mainly involved in this interaction.
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Differential antagonism of the stimulant effects of MK-801 and methamphetamine by Ceruletide: evaluation by discrete shuttle avoidance response in mice.
Japanese journal of pharmacology, 1991Co-Authors: Hisashi Kuribara, Sakutaro TadokoroAbstract:Abstract. A noncompetitive NMDA antagonist MK-801 (0.03-0.3 mg/kg, i.p.) increased the response rate of mice trained under the discrete shuttle avoidance situation to a degree similar to the increase by methamphetamine (0.1-1 mg/kg. i.p.). The cholecystokinin-like decapeptide Ceruletide significantly reduced the response-increasing effect of MK-801 (0.1 mg/kg) at 0.001 μg/kg; however, only 10 μg/kg of Ceruletide, which per se inhibited the response, attenuated that of methamphetamine (0.3 mg/kg). The coadministration of MK-801 (0.1 mg/kg) and methamphetamine (0.3 mg/kg) produced no potentiation of the effect, and almost the same effect was maintained even after the additional administration of Ceruletide (0.1 μg/kg).