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M Ukai

Publications and source records attributed to M Ukai.

At least 55 records · Page 3Linked to original sources
PubMed1995

Cholinergic receptor agonists inhibit pirenzepine-induced dysfunction of spontaneous alternation performance in the mouse.

1. The present study was designed to examine the effects of intracerebroventricular injection of several cholinergic drugs on the impairment of spontaneous alternation performance induced by the M1-selective muscarinic receptor antagonist pirenzepine. 2. Pirenzepine (3 and 10 micrograms) significantly reduced spontaneous alteration performance related to working memory without producing any marked increase in total arm entries, which are considered to reflect locomotor activity. 3. Physostigmine (3.47 micrograms), a cholinesterase inhibitor, and McN-A-343 (20 micrograms), and M1-selective muscarinic receptor agonist, significantly improved the pirenzepine (3 micrograms)-induced impairment of spontaneous alternation performance, although oxotremorine (0.68 microgram), a nonselective muscarinic receptor agonist, showed a tendency to reverse the pirenzepine (3 micrograms)-induced impairment. 4. These findings suggest that the blockade of muscarinic M1 but not M2 receptors results in the impairment of spontaneous alternation performance associated with working memory.

(4-(m-Chlorophenylcarbamoyloxy)-2-butynyl)trimethy↗
PubMed1994

Effects of several amnesic drugs on the habituation of exploratory activity in mice as indexed by horizontal and vertical activities.

1. The effects of several drugs on the habituation of exploratory activity in mice were investigated by using animal movement analyzing systems which could detect horizontal and vertical activities. 2. Habituation was regarded as the difference between exploratory activity measured first (session 1) and that measured second (session 2). 3. Scopolamine (1, 3 and/or 6 mg/kg), pirenzepine (20 and 40 micrograms) injected immediately after session 1, cycloheximide (30 mg/kg), diazepam (1, 2 and/or 4 mg/kg) and dizocilpine (0.05, 0.1 and/or 0.2 mg/kg), unlike butylscopolamine (1, 3 and 6 mg/kg) or haloperidol (0.2 and 0.4 mg/kg), significantly increased horizontal activity but not always vertical activity in session 2. 4. From the results obtained, it appears that the increase in horizontal activity in session 2 is more appropriate as an indicator of the impairments of memory processes than that in vertical activity.

Amnesia↗
PubMed1994

Effects of human epidermal growth factor on passive avoidance and habituation learning in mice.

1. Human epidermal growth factor (hEGF:0.02-2.0 micrograms) did not affect passive avoidance response or habituation learning when given before or immediately after training, or before retention. 2. hEGF (0.02-2.0 micrograms) failed to influence the scopolamine- or electroconvulsive shock-induced shortening of step-down latency in passive avoidance response when given before or immediately after training, or before retention. 3. These results suggest that the acute administration of hEGF does not affect memory processes as indexed by passive avoidance or habituation learning in normal or amnesic mice.

Amnesia↗
PubMed1994

Characterization of the effects of scopolamine on the habituation of exploratory activity: differential effects of oxotremorine and physostigmine.

1. Habituation was regarded as a difference between exploratory activity measured first (session 1) and that measured second (session 2) in a novel environment. 2. Scopolamine (1.0 mg/kg) significantly increased the horizontal activity in sessions 1 and 2 when administered prior to session 1, resulting in the impairment of habituation. 3. Haloperidol (0.2 mg/kg) inhibited scopolamine-induced hypermotility in session 1, but it did not inhibit the scopolamine-induced impairment of habituation in session 2. 4. The direct cholinergic agonist oxotremorine (0.03 mg/kg), unlike the cholinesterase inhibitor physostigmine, significantly inhibited the scopolamine-induced impairment of habituation in the horizontal and vertical activities. 5. These results suggest that the direct stimulation of cholinergic receptors is more effective for scopolamine-induced amnesia than the indirect stimulation of cholinergic receptors by cholinesterase inhibitors in the habituation task.

Amnesia↗
PubMed1994

Dynorphin A-(1-13) potently improves galanin-induced impairment of memory processes in mice.

The present study examined the effects of intracerebroventricular injection of dynorphin A-(1-13) on memory processes by using the passive avoidance task in mice. Galanin (0.3 microgram) significantly shortened the step-down latency when given 15 min before retention tests. Although dynorphin A-(1-13) (1 or 3 micrograms) did not prolong the step-down latency induced by weaker electroshocks, it inhibited the galanin (0.3 micrograms)-induced shortening of step-down latency. The effects of dynorphin A-(1-13) (3 micrograms) on the galanin-induced shortening of step-down latency were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms), a kappa-selective opioid antagonist. These results strongly suggest that dynorphin A-(1-13) attenuates galanin-induced impairment of memory processes through the mediation of kappa-opioid receptors.

Amnesia↗
PubMed1994

Binding and aggregation of human gamma-globulin by cis-diamminedichloroplatinum(II) through disulfide bond.

The incubation of gamma-globulin with cis-diamminedichloroplatinum (II) (cis-DDP) resulted in gradual formation of insoluble aggregates. Since the precipitates, composed of polymerized gamma-globulin and cis-DDP, were completely solubilized with urea, the reaction mixture containing precipitate was examined in terms of the binding of cis-DDP and the effect on disulfide (S-S) bonds in the gamma-globulin. When gamma-globulin was incubated with 30 molar excess cis-DDP at pH 7.4 and 37 degrees C, cis-DDP gradually bound to as much as 12 mol per mol of gamma-globulin in 14 d. Concurrently, about four disulfide bonds were cleaved without reaching a certain plateau. An sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the aggregated gamma-globulin induced by cis-DDP was significantly different from that of the heat-denaturated aggregate form or the reduced form by sulfitolysis. The aquated complexes of cis-DDP also produced an insoluble precipitate and affected the S-S bond to a greater extent than the parent drug.

Cisplatin↗
PubMed1994

Hemodynamic effects of the calcium channel blocker pranidipine on exercise-induced angina.

Hemodynamic effects of a newly developed calcium channel blocker, pranidipine, on dynamic exercise-induced angina were investigated. Ten patients with stable effort angina pectoris underwent symptom-limited bicycle ergometer exercise testings before and after a single oral administration of pranidipine, and effects of pranidipine on systemic, cardiac and coronary hemo-dynamics induced by dynamic exercise were evaluated invasively. Pranidipine administration reduced systemic vascular resistance (from 1,764 +/- 109 to 1,115 +/- 60 dynes.sec/cm5; p < 0.01 at test, and from 1,120 +/- 102 to 795 +/- 62 dynes.sec/cm5; p < 0.05 at peak exercise) and mean arterial pressure (from 93 +/- 5 to 76 +/- 3 mmHg; p < 0.01 at test, and from 85 +/- 7 to 72 +/- 6 mmHg; p < 0.05 at peak exercise) with the increase in heart rate and cardiac index throughout exercise. Pranidipine also decreased coronary vascular resistance from 1.29 +/- 0.21 to 0.89 +/- 0.17 mmHg/ml/min (p < 0.05) at resting condition. At peak exercise, rate-pressure product and myocardial oxygen consumption decreased (from 237 +/- 21 to 215 +/- 18 x 10(2); p < 0.05, and from 31.3 +/- 7.5 to 21.7 +/- 3.9 ml/min; p < 0.05, respectively), while coronary vascular resistance did not change significantly. Furthermore, pranidipine mitigated ST-segment depression and elevation of pulmonary artery wedge pressure at peak exercise (from 0.20 +/- 0.03 to 0.13 +/- 0.02 mV; p < 0.01, and from 25 +/- 3 to 11 +/- 2 mmHg; p < 0.01, respectively). These results suggest that the major therapeutic effects of pranidipine for dynamic exercise-induced angina would be to reduce myocardial oxygen demand by improving peripheral circulation and reducing preload and afterload.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

Dynorphin A-(1-13) potently improves the impairment of spontaneous alternation performance induced by the mu-selective opioid receptor agonist DAMGO in mice.

The effects of i.c.v. injection of the mu-selective opioid receptor agonist DAMGO and the effects of its combination with the endogenous kappa-opioid receptor agonist dynorphin A-(1-13) on memory processes were examined in mice, using spontaneous alternation performance associated with working memory in a Y-maze. DAMGO (10 and/or 30 ng) impaired spontaneous alternation performance and increased total arm entries, which are considered to reflect locomotor activity. beta-Funaltrexamine (5 micrograms, i.c.v.), a mu-selective opioid receptor antagonist, almost completely antagonized the impairment of alternation performance induced by DAMGO (10 ng). Physostigmine (0.1 mg/kg, i.p.), a cholinesterase inhibitor, improved the DAMGO (10 ng)-induced impairment of alternation performance. Dynorphin A-(1-13) (1, 3 and 10 micrograms, i.c.v.) alone was without significant effects on alternation performance. On the other hand, dynorphin A-(1-13) (3 and 10 micrograms) significantly improved the impairment of spontaneous alternation performance induced by DAMGO (10 ng). The effects of dynorphin A-(1-13) (3 micrograms) on the DAMGO-induced impairment of spontaneous alternation were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-selective opioid receptor antagonist. The present results demonstrate that DAMGO impairs alternation performance by activating mu-opioid receptors, whereas dynorphin A-(1-13) attenuates the DAMGO-induced impairment of alternation performance through the mediation of kappa-opioid receptors. These findings suggest that mu- and kappa-opioid systems are fully involved in memory function and have opposite effects on spontaneous alternation performance as it is reflected by working memory in mice.

Analgesics↗
PubMed1994

Opioid peptides selective for receptor types modulate cocaine-induced behavioral responses in mice.

The effects of intracerebroventricular injection of mu-, kappa- and delta-selective opioid agonists on cocaine-induced behavior were investigated in mice using multidimensional behavioral analysis. Cocaine (3.0 mg/kg) produced a marked increase in linear locomotion, circling, rearing and/or grooming, although the mu-opioid agonist [D-Ala2, NMePhe4, Gly-ol] enkephalin (DAMGO) (0.003 and 0.01 microgram), the kappa-opioid agonist dynorphin A- (1-13) (3.0 and 12.5 micrograms) or the delta-opioid agonist [D-Pen2, L-Pen5]enkephalin (DPLPE) (0.3 and 1.0 micrograms) did not significantly affect behavioral responses. DAMGO (0.003 and 0.01 microgram) and dynorphin A- (1-13) (12.5 micrograms) inhibited the cocaine (3.0 mg/kg)-induced increase in linear locomotion, circling and/or rearing. In contrast, DPLPE (1.0 micrograms) enhanced the cocaine (3.0 mg/kg)-induced increase in circling. The effects of DAMGO (0.003 microgram), dynorphin A- (1-13) (12.5 micrograms) and DPLPE (1.0 micrograms) were fully reversed by receptor-selective opioid antagonists, such as beta-funaltrexamine (5.0 micrograms), Mr2266 (5.6 mg/kg) and naltrindole (10.0 mg/kg), respectively. These results suggest that the activation of mu- and kappa-opioid receptors inhibits cocaine-induced behavior, while that of delta-opioid receptors enhances the behavior.

Animals↗
PubMed1994

Differential modulation of behavioral responses by [D-Ala2, NMePhe4, Gly-ol]enkephalin, [D-Ala2] deltorphin II and [D-Pen2, L-Pen5]enkephalin in the mouse.

The effects of [D-Ala2, NMePhe4, Gly-ol]enkephalin (DAMGO), a mu-selective opioid receptor agonist, [D-Ala2]deltorphin II (DELT) and [D-Pen2, L-Pen5]enkephalin (DPLPE), delta-selective opioid receptor agonists, on different behavioral responses were investigated in mice by multidimensional behavioral analyses. DAMGO (0.1 and/or 0.3 microgram) produced a marked increase in circling, rearing and grooming within 15-30 min after the start of behavioral measurements. DELT (0.3, 1.0 and/or 3.0 micrograms) produced a significant increase in linear locomotion and circling within 15-30 min after the start of behavioral measurements, whereas DPLPE (10.0 micrograms) increased only circling. The behavioral effects of DAMGO, DELT or DPLPE were almost completely antagonized by beta-funaltrexamine (2.5 and 5.0 micrograms) or naltrindole (3.0 and 10.0 mg/kg). These results suggest that opioid peptides selective for receptor types elicit different behavioral responses in mice. Moreover, the different behavioral effects between DPLPE and DELT may be due to the delta opioid receptor subtypes such as delta-1 and delta-2.

Analysis of Variance↗
PubMed1993

Dynorphin A-(1-13) attenuates basal forebrain-lesion-induced amnesia in rats.

The effects of dynorphin A-(1-13), an endogenous kappa opioid agonist, on basal forebrain (BF)-lesion-induced amnesia in rats were investigated using step-through-type passive avoidance task. The BF was lesioned by injecting the cholinergic neurotoxin ibotenic acid (6 micrograms/side). The number of rats achieving the cut-off time (600 s) of step-through latency (STL) in BF-lesioned group significantly decreased as compared with that in sham-operated group. Dynorphin A-(1-13) (0.3 micrograms) significantly increased the number of rats achieving the cut-off time of STL in BF-lesioned rats. These results suggest that dynorphins play an improving role in the impairment of memory processes in BF-lesioned rats.

Alzheimer Disease↗
PubMed1993

Dopaminergic involvement in the improving effects of dynorphin A-(1-13) on scopolamine-induced impairment of alternation performance.

The present study was designed to clarify whether dopamine systems are involved in the effect of dynorphin A-(1-13), an endogenous kappa-opioid receptor agonist, on the scopolamine-induced impairment of spontaneous alternation performance related to working memory in mice. Sulpiride (10 and/or 30 mg/kg), a dopamine D2-selective antagonist, markedly improved the impairment of alternation performance and significantly reduced the increase in total arm entries (i.e. locomotor activity) induced by scopolamine (1 mg/kg). In contrast, SCH 23390 (0.01, 0.03 and 0.1 mg/kg), a dopamine D1-selective antagonist, did not influence the impairment of alternation performance, whereas it dose dependently reduced total arm entries in scopolamine-treated mice RU 24213 (1 mg/kg), a dopamine D2-selective agonist, almost completely reversed the improving effect of dynorphin A-(1-13) (3 micrograms) on the scopolamine-induced impairment of alternation performance and reduced total arm entries, although it was without effects on behavioral responses in normal mice. However, SKF 38393 (3 and 10 mg/kg), a dopamine D1-selective agonist, failed to change alternation performance or total arm entries in normal or scopolamine-treated mice. These findings suggest that the impairment of spontaneous alternation performance induced by scopolamine is improved by the blockade of dopamine D2 receptors. Furthermore, the improving effect of dynorphin A-(1-13) on the scopolamine-induced impairment of spontaneous alternation performance may be based upon the inhibition of dopaminergic activity through the mediation of kappa-opioid receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1993

U-50,488H, a kappa-opioid receptor agonist, markedly prevents memory dysfunctions induced by transient cerebral ischemia in mice.

Transient ischemia produced marked memory dysfunctions in mice on three different tasks, spontaneous alternation, elevated plus-maze and passive avoidance, as tested 1, 1-2, and 2-3 days after ischemic insult, respectively. U-50,488H, a kappa-opioid receptor agonist, administered 20 min before ischemic insult markedly prevented the impairment of spontaneous alternation, the prolongation of transfer latency in elevated-plus maze and the shortening of step-through latency in passive avoidance induced by transient ischemia. The protective effect of U-50,488H (30 mg/kg) on ischemia-induced memory dysfunctions observed in the three tasks was almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-selective opioid antagonist. Although U-50,488H (30 mg/kg) did not affect body temperature in sham mice, it blocked hypothermia induced by ischemic insult. These results suggest that the protective effect of U-50,488H on memory dysfunctions in ischemic mice is associated with the activation of kappa-opioid receptors and is not based upon hypothermia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1993

Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog, impairs memory consolidation in mice.

Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog with high selectivity and affinity for mu-opioid receptors, was administered intracerebroventricularly to mice before or immediately after training in a one-trial step-down type passive avoidance task. The pre- and post-training administration of TAPA (0.3 and/or 3 ng) impaired retention performance 24 h after training. In particular, the post-training administration of TAPA was much more effective because a lower dose (0.3 ng) of TAPA exclusively inhibited retention performance. The amnesic effects of TAPA were reversed by the mu-selective opioid antagonist beta-funaltrexamine (5 micrograms, i.c.v.). In addition, TAPA (0.3 and 3 ng) had no effects on nociceptive responses in a tail-flick test or on behavioral responses to electric shock during training. These results suggest that activation of mu-opioid receptors impairs passive avoidance learning, resulting in a dysfunction of memory consolidation, without affecting other behavioral responses.

Amino Acid Sequence↗
PubMed1993

Dynorphin A-(1-13) markedly improves scopolamine-induced impairment of spontaneous alternation performance in mice.

The effect of intracerebroventricular (i.c.v.) injection of dynorphin A-(1-13) on the memory process was examined in mice, using spontaneous alternation performance related to working memory in a Y-maze. Dynorphin A-(1-13) (1, 3 and 10 micrograms) influenced neither spontaneous alternation performance nor total arm entries, which are considered to reflect locomotor activity. In contrast, dynorphin A-(1-13) (3 and 10 micrograms) significantly improved the impairment of spontaneously alternation performance induced by scopolamine (1 mg/kg s.c.). Simultaneously, the scopolamine-induced increase in total arm entries was markedly attenuated by dynorphin A-(1-13) (10 micrograms). The effect of dynorphin A-(1-13) (3 micrograms) on the scopolamine-induced impairment of spontaneous alternation was almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms i.c.v.), a kappa-selective opioid antagonist. These findings suggest that dynorphin A-(1-13) improves through the mediation of kappa-opioid receptors the scopolamine-induced impairment of spontaneous alternation performance associated with working memory.

Analysis of Variance↗
PubMed1993

Dynorphin A-(1-13) potently prevents memory dysfunctions induced by transient cerebral ischemia in mice.

The effect of dynorphin A-(1-13), an endogenous kappa-opioid receptor agonist, on memory dysfunctions induced by transient cerebral ischemia in mice was investigated by using three different tasks, namely, spontaneous alternation, elevated plus-maze performance, and passive avoidance behavior. Transient ischemia produced a marked memory dysfunction in mice, as assessed in the three tasks, which were carried out consecutively 1 to 3 days after the ischemic insult. The i.c.v. injection of dynorphin A-(1-13) before the ischemic insult potently prevented the impairment of spontaneous alternations, the prolongation of transfer latency in the elevated plus-maze and the shortening of step-through latency in the passive avoidance task induced by transient ischemia. Dynorphin A-(1-13) (10 micrograms), however, did not affect the body temperature of the sham-operated or the ischemic mice. The protective effect of dynorphin A-(1-13) (10 micrograms) on ischemia-induced memory dysfunctions observed in the three tasks was almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-selective opioid receptor antagonist. These results suggest that dynorphin A-(1-13) prevents memory dysfunctions in ischemic mice through the activation of kappa-opioid receptors.

Animals↗
PubMed1993

Cocaine-like discriminative stimulus properties of the delta-selective opioid receptor agonist, [D-Pen2,L-Pen5]enkephalin, in the rat.

The delta-selective opioid receptor agonist, [D-Pen2,L-Pen5]enkephalin (DPLPE) (10 micrograms i.c.v.), fully generalized to cocaine cue in the rat trained to discriminate 10 mg/kg of cocaine from vehicle. The cocaine-like discriminative stimulus effects of DPLPE were almost completely reversed by naltrindole (56 micrograms i.c.v.), a delta-selective opioid receptor antagonist. In contrast, the mu-selective opioid receptor agonist [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.03-0.3 micrograms i.c.v.) failed to generalize to cocaine cue. These results suggest that the discriminative stimulus effects of cocaine are mediated through the activation of delta-opioid receptors.

Animals↗