Biomedical subjects

T Nabeshima

Publications and source records attributed to T Nabeshima.

At least 289 records · Page 16Linked to original sources

PubMed1991

Effects of successive carbon monoxide exposures on delayed neuronal death in mice under the maintenance of normal body temperature.

The 3 time carbon monoxide (CO) exposures potentiated the delayed neuronal death (DND) in comparison with that induced by single CO exposure. Deterioration of DND induced by CO exposures was observed when normal body temperature was maintained during the exposures, since CO exposure fell the body temperature to about 34 degrees C. Pretreatment with noncompetitive NMDA receptor antagonist, MK-801 (30 nmol/mouse), ameliorated DND induced by successive CO exposures under the maintenance of normal body temperature. These results suggest that the mice exposed successively to CO under the maintenance of normal body temperature is a useful hypoxic model.

Animals↗

PubMed1991

Involvement of the cholinergic neuronal system and benzodiazepine receptors in alcohol-induced amnesia.

We investigated the involvement of the GABAergic and cholinergic neuronal systems and benzodiazepine (BZP) receptors in ethanol-induced amnesia using a passive avoidance task. Pretraining administration of ethanol impaired the passive avoidance response. The BZP agonist chlordiazepoxide potentiated the amnesia, while the GABA antagonists bicuculline and picrotoxin failed to affect it. The acetylcholine esterase inhibitor physostigmine partially attenuated the ethanol-induced amnesia. These results suggest that ethanol-induced amnesia is related to BZP receptors and a dysfunction of the cholinergic neuronal system.

Amnesia↗

PubMed1991

Memory impairment and morphological changes in rats induced by active fragment of anti-nerve growth factor-antibody.

Treatment of rats with a specific Fab' fragment of anti-nerve growth factor (NGF)-antibody (anti-NGF, 12, 120 and 400 micrograms/4 weeks, i.c.v.) impaired their learning ability. The distance of swimming of anti-NGF-treated rats in a water maze was shortened more slowly by training than that of control rats. Anti-NGF treatment altered the staining of nuclei of cells in the hippocampus, parietal cortex and dentate gyrus with hematoxylin. It is suggested that the anti-NGF-induced amnesia could be due to change in nuclear morphology.

Animals↗

PubMed1991

Utility of an elevated plus-maze for dissociation of amnesic and behavioral effects of drugs in mice.

Learning and memory were previously evaluated by using the elevated plus-maze test in mice. We investigated whether this method could be used for the evaluation of amnesic properties of drugs, including those which alter behavior on the first (training) trial. Six drugs of different types, scopolamine, MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate), diazepam, butylscopolamine, methamphetamine and haloperidol were administered before training. The transfer latency of vehicle-treated mice on retention testing was significantly shorter than that on training. The transfer latencies in mice given scopolamine (1 and 3 mg/kg s.c.), butylscopolamine (6 mg/kg s.c.), methamphetamine (2 and 4 mg/kg i.p.), or haloperidol (0.4 mg/kg i.p.) were significantly prolonged on training compared with those of the corresponding vehicle groups. However, significant prolongation of the transfer latency in the retention test, compared to the vehicle groups, was observed only in mice given scopolamine (3 mg/kg s.c.), MK-801 (0.1 and 0.15 mg/kg i.v.), diazepam (4 mg/kg i.p.), or methamphetamine (4 mg/kg i.p.). These results suggested that the prolongation of the transfer latency on retention testing in the plus-maze method might be used as an indicator for impairment of learning and memory induced by the drugs which have amnesic properties, and is not related to the change in transfer latency on training.

Amnesia↗

PubMed1991

Interaction between enkephalinergic and dopaminergic systems in stressful situations.

Mice exhibit a marked suppression of mobility when they are placed in the same cage in which they had previously received an electric shock. This suppression of motility is believed to be a stress-induced response. [D-Ala2,Met5]enkephalinamide (DAMEA, 40 and 80 nmol i.c.v.), a derivative resistant to [Met5]enkephalin-degrading enzyme activity, significantly attenuated the conditioned suppression of motility. The attenuation of conditioned suppression of motility induced by DAMEA was antagonized not only by naloxone (0.1 mg/kg s.c.), but also by 6-hydroxydopamine (6-OHDA, 100 micrograms/mouse, i.c.v.)-induced lesions of dopaminergic (DAergic) neurons. Pimozide (100 micrograms/kg i.p.) and a low dose of apomorphine (50 micrograms/kg s.c.) also inhibited the effect of DAMEA. In addition, DAMEA reversed the decrease in DA turnover in the striatum in the conditioned suppression group. These results suggest that the attenuation of conditioned suppression of motility induced by activation of the [Met5]enkephalinergic system may be related to the striatal DAergic system.

Animals↗

PubMed1991

Staurosporine, a protein kinase inhibitor, attenuates basal forebrain-lesion-induced amnesia and cholinergic neuronal deficit.

We have investigated whether administration of staurosporine, which has been reported to induce differentiation in the human neuroblastoma cell in vitro, attenuates amnesia induced by basal forebrain lesion in rats. Multiple dosage of staurosporine at the doses of 0.05 and 0.1 mg/kg (i.p.) attenuated the impaired performance of the water maze task. Moreover, staurosporine (0.1 mg/kg) reversed the decrease of choline acetyltransferase activity in the fronto-parietal cortex. These results suggest that staurosporine attenuates amnesia through reversal of deficits in cholinergic neurons induced by basal forebrain lesion, and that neurotrophic factor-like substances may open the way for novel therapeutic approaches to Alzheimer's disease.

Alkaloids↗

PubMed1991

Dose-dependent pharmacokinetics of enprofylline and its renal handling in rats.

The effect of dosage on the pharmacokinetics of the potent bronchodilator enprofylline (3-propylxanthine; PX) and its renal handling were investigated in rats. Enprofylline (PX) was administered iv in dosages of 2.5, 10, 20, and 40 mg/kg, and PX concentration in plasma and urine was determined by HPLC. The pharmacokinetic parameters were estimated by model-independent methods. The disappearance of PX from plasma was delayed as dosage was increased. The corresponding pharmacokinetic parameters also showed dose dependency; increases in the volume of distribution (Vd) and mean residence time (MRT) and a decrease in total body clearance (CLT) were observed as dosage was increased from 2.5 to 40 mg/kg. Approximately 80% of the dose, however, was excreted in urine as unchanged PX. Plasma protein binding studies of PX showed concentration dependency and allowed determination of binding parameters, with an apparent dissociation constant (Kd) of 162.50 microM and a binding capacity (nP) of 565.23 microM. Some pharmacokinetic parameters for unbound PX calculated by total plasma concentration and binding parameters also showed dose-dependent characteristics. However, no significant change in Vd for unbound PX was observed among administered doses, indicating that the distribution of PX into the body tissues is not changed by an increase in dosage. Renal clearance of unbound PX significantly increased as plasma concentration decreased. The maximum transport capacity (Vmax) and the Michaelis-Menten constant (Km) for tubular secretion were 60.53 micrograms/min and 2.27 micrograms/mL, respectively. The aim of the present study is to demonstrate that both saturable tubular secretion and concentration-dependent protein binding are responsible for the dose-dependent pharmacokinetics of PX in rats.

Animals↗

PubMed1991

Pharmacokinetic characteristics of N7-substituted theophylline derivatives and their interaction with quinolone in rats.

Disposition of diprophylline (DPP) and proxyphylline (PXP) and the effect of enoxacin on their disposition were investigated in rats. Concentrations of the two drugs in plasma and urine were measured by HPLC. The pharmacokinetic parameters of the two drugs were estimated by model-independent methods. Although the chemical structures of the two drugs are very similar, remarkable differences in the disposition of the two drugs were observed. Total body clearance (CLT) of DPP was 1.77 L/h/kg, which was sevenfold greater than that of PXP (0.26 L/h/kg). Diprophylline was excreted in an almost completely unchanged form in the urine, but only 50% of PXP was excreted. However, no binding of either drug to proteins in rat plasma was observed. The DPP renal clearance (CLR) was 1.75 L/h/kg, approximately 13-fold the CLR for PXP (0.13 L/h/kg) and sevenfold the rat glomerular filtration rate. This study indicates that in rats, DPP is mainly excreted by active tubular secretion and that renal tubular reabsorption contributes to renal excretion of PXP with glomerular filtration. No significant changes in any pharmacokinetic parameters of the two drugs were observed when they were coadministered with enoxacin, compared with the drug administered alone, suggesting that enoxacin had no effect on the pharmacokinetics of either drug.

Aminophylline↗

PubMed1991

Involvement of GABAergic systems in benzodiazepine-induced impairment of passive avoidance learning in mice.

The possible involvement of GABAergic neuronal systems in benzodiazepine (BZP)-induced impairment of a passive avoidance response was investigated. Chlordiazepoxide (CDP) impaired passive avoidance when administered prior to training. The CDP-induced impairment was antagonized by pretreatment with picrotoxin, but not by pretreatment with bicuculline or post-training administration of picrotoxin. On the contrary, when combined with muscimol, the dose at which CDP impaired the response was lower than the dose at which it did so alone. The synergy of muscimol and CDP was attenuated by pretreatment with flumazenil or bicuculline. From these results, we conclude that GABAergic systems play an important role in the BZP-induced impairment of passive avoidance.

Animals↗

PubMed1991

Pharmacokinetic and pharmacodynamic properties of some phencyclidine analogs in rats.

The pharmacodynamics and pharmacokinetics of three phencyclidine analogs, differing from phencyclidine (PCP) only in the nature of the amine structure, were determined after intravenous doses of equimolar amounts to rats. The purpose of the study was to assess the role of pharmacokinetics in the in vivo potency of the compounds. The compounds examined were phenylcyclohexyl-pyrrolidine (PCPY), diethylamine (PCDE), ethylamine (PCE), and phencyclohexylamine (PCA). The behavior responses monitored included ataxia and others previously shown to be characteristic of PCP. In contrast to their relative affinities for the MK 801 binding site, the behavioral potencies of PCE, PCDE and PCPY were comparable to PCP. The major discrepancy occurred with PCDE, whose affinity for the NMDA receptor was 1/20th of PCP. The pharmacokinetic studies showed that the discrepancy between in vivo and in vitro activity of PCDE could be partially accounted for by its conversion to PCE, a relatively potent PCP-like agent.

Animals↗

PubMed1991

Naftidrofuryl oxalate, nootropic effects on the scopolamine- and the basal forebrain lesion-induced amnesia in rats.

We studied the effects of naftidrofuryl oxalate on scopolamine- and basal forebrain (BF) lesion-induced amnesia using passive avoidance and multiple T-maze tasks, in comparison with Ca-hopantenate and physostigmine in rats. In the passive avoidance task, one-week treatment with naftidrofuryl oxalate (12.5 and 25 mg/kg, IP) ameliorated BF lesion-induced amnesia. The multiple T-maze task was done with two training sessions per day for five continuous days. We measured the number of errors made from start box to goal box. Naftidrofuryl oxalate (12.5 mg/kg, IP, b.i.d.) and physostigmine (0.1 mg/kg, IP, b.i.d.) attenuated scopolamine- and BF lesion-induced amnesia. However, treatment with naftidrofuryl oxalate for one week failed to inhibit the decrease of the choline acetyltransferase induced by the BF lesion. Ca-hopantenate did not show attenuation of amnesia induced by the scopolamine or BF lesion. These results suggest that naftidrofuryl oxalate enhances the storage of spatial information, and that the nootropic effects of naftidrofuryl oxalate may be produced by an indirect activation of the cholinergic system through serotonergic neuronal systems.

Amnesia↗

PubMed1991

Structure-related inhibitory effect of quinolones on alkyl-xanthine elimination in rats.

To investigate the relationship between the chemical structures of quinolones, enoxacin (ENX) and its analogues, and their metabolic inhibitory effects on theophylline, a xanthine derivative closely related to theophylline, 1-methyl-3-propylxanthine (MPX), was used as a model of theophylline in rats. The disappearance of MPX from plasma was significantly delayed by treatment with ENX and analogue A (derivatives without substituent group at both 3'- and 5'- carbon atom in the piperazinyl ring): total body clearance of MPX was significantly decreased by approximately 50%. However, analogue A was converted into ENX in the rat body (about 14% of dose). Analogues B and C (derivatives with substituent group at 3'- or 5'-carbon atom in the piperazinyl ring) had little or no effect on MPX disposition. No significant change in the volume of distribution of MPX was observed after coadministration with these quinolones. The results of this study indicate that the substitutions on 3' and 5'-carbon atoms of piperazinyl ring at 7-position of the quinolone molecule may play important role in the inhibition of theophylline metabolism.

Animals↗

PubMed1991

Structure-pharmacokinetic relationships among the N1,N3-alkylxanthines in rats.

The pharmacokinetics of four N3-alkylxanthine and four N1-methyl-N3-alkylxanthine derivatives has been investigated in rats after intravenous administration of the individual alkylxanthines. The concentration of N1,N3-alkylxanthine in plasma and urine was determined by HPLC. A one-compartment model adequately described the plasma concentration time data. The steady-state volume of distribution (Vss) was calculated using model-independent methods. The relation between Vss and unbound drug fraction in plasma (fu) was significantly correlated (Vss = 0.844fu + 0.119; r = 0.999, P less than 0.01), indicating that the differences in fu among these xanthine derivatives is mainly responsible for differences in Vss. The decrease in Vss and increase in plasma protein binding with lipophilicity reflected a relatively constant tissue affinity. The total body clearance increased with lipophilicity with the exception of the first three lower congeners which were almost completely excreted unchanged in urine, mainly via active tubular secretion. Renal elimination was markedly reduced by the presence of a methyl group at the N1-position. Renal clearance decreased with increasing lipophilicity, due to increased tubular reabsorption whereas non-renal (hepatic) clearance increased with increasing lipophilicity.

Animals↗

PubMed1991

Aged-related changes in learning and memory, choline acetyltransferase activity and number of neuronal cells in rats.

In a water maze task, the goal latency and distance of swimming onto the platform of aged rats (24 months old) were slowly shortened by repeated training compared with those of young rats (8 weeks old). A significant decrease in choline acetyltransferase activity in the frontal cortex, parietal cortex and striatum was observed in aged rats. Moreover, the number of neuronal cells in the hippocampal CA1 subfield and dentate gyrus of aged rats was smaller than that of young rats. The atrophy of striatal cells was observed. These results suggest that age-related delay of acquisition is due to the above-mentioned biochemical and histological changes, and that rates of aging in biochemical and morphological parameters are different in the discrete brain areas.

Aging↗

PubMed1991

Impairment of active avoidance response in rats with continuous infusion of quinolinic acid into the lateral ventricle.

Continuous infusion of quinolinic acid (QA) at low doses into the lateral ventricle has been previously shown to cause a reduction of the hippocampal and cortical ChAT activities in rats although GAD activities were unchanged. In the present study, we have studied behavioral changes in rats with continuous infusion of QA in an active avoidance task. Acquisition of active avoidance was significantly impaired in rats with QA infusion compared to control. These results suggest that continuous infusion of QA is a useful technique for the study of chronic neurodegenerative diseases associated with memory impairment.

Animals↗

PubMed1991

The effect of tacrine (THA) on cycloheximide- and basal forebrain lesion-induced memory deficit in rats.

The effects of 9-amino-1,2,3,4-tetrahydroacridine (tacrine), an active acetylcholinesterase inhibitor, on cycloheximide- and basal forebrain (BF) lesion-induced memory deficit in the water maze and passive avoidance task were investigated. While cycloheximide (1.5 mg/kg, s.c.) produced amnesia in the passive avoidance task, chronic administration of tacrine (1, 3 and 10 mg/kg, once a day for 1 week) improved the amnesia. BF lesion produced amnesia in both the water maze and passive avoidance tasks. Chronic tacrine (0.1-3 mg/kg, passive avoidance task, or 0.3 mg/kg, water maze task, once a day for 1 week) improved BF lesion-induced amnesia in the passive avoidance and water maze tasks. These results suggest that tacrine may be useful for senile dementia.

Administration, Oral↗

PubMed1991

Carbon monoxide-induced delayed amnesia, delayed neuronal death and change in acetylcholine concentration in mice.

We investigated the interrelationship of delayed amnesia, delayed neuronal death and changes in acetylcholine concentration induced by carbon monoxide (CO)-exposure in mice. In the test for retention of the passive avoidance task, amnesia was observed 5 and 7 days after CO-exposure when the mice were exposed to CO 1 day after training; in the case when the mice were exposed to CO 5 and 7 days before training, amnesia was also observed in a retention test given 1 day after training. The number of pyramidal cells in the hippocampal CA1 subfield was lower than that of the control 3, 5 and 7 days after CO-exposure. But the neurodegeneration in the parietal cortex, area 1, was not observed until 7 days after CO-exposure. The findings indicated that the amnesia and the neuronal death were produced after a delay when the mice were exposed to CO. In addition, the delayed amnesia was closely related to the delayed neuronal death in the hippocampal CA1 subfield. Moreover, [3H]glutamate and [3H]glycine binding sites did not change after CO-exposure but, 7 days after CO-exposure, the concentration of acetylcholine and the binding of [3H]quinuclidinyl benzilate in the frontal cortex and the striatum were found to have significantly changed, but those in the hippocampus did not show significant change. Therefore, we suggest that delayed amnesia induced by CO-exposure may result from delayed neuronal death in the hippocampal CA1 subfield and dysfunction in the acetylcholinergic neurons, in the frontal cortex, the striatum and/or the hippocampus.

Acetylcholine↗

PubMed1991

Memory impairment and morphological changes in rats after continuous infusion of active fragment of anti-nerve growth factor-antibody.

We report here that the specific Fab' fragment of anti-nerve growth factor (NGF)-antibody (anti-NGF, 12, 120 and 400 micrograms/4 weeks, i.c.v.) impairs learning and memory. The goal latency of the control rats in water maze task was rapidly shortened by training compared to those of the anti-NGF-treated rats. The degree of reduction in movement counts of the anti-NGF-treated rats in habituation task was significantly smaller than that of the control rats. However, the step-through latency of the anti-NGF-treated rats was not significantly shorter than that of the control rats. With regard to the choline acetyltransferase activity, no effects were observed in any of the brain regions. Anti-NGF treatment altered nuclear morphology in the hippocampus and parietal cortex. As a result, it seems that the anti-NGF-induced amnesia could be due to an impairment of nuclear morphology.

Analysis of Variance↗