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M Ukai

Publications and source records attributed to M Ukai.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effects of the dopamine D3 receptor agonist, R(+)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin, on memory processes in mice.

The putative dopamine D3 receptor agonist, R(+)-7-hydroxy-N,N-di-n-propyl-2-aminotetralin (R(+)-7-OH-DPAT) (0.1-100 microg/kg, s.c.), administered before training, immediately after training, and before retention significantly shortened step-down latency of passive avoidance learning, indicating the amnesic effects of R(+)-7-OH-DPAT. Neither the dopamine D1 receptor antagonist, R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzaz epine maleate R(+)-SCH23390) (2.5 and 5 microg/kg, i.p.), nor the dopamine D2 receptor antagonist, S(-)-sulpiride (10 and 30 mg/kg, i.p.), markedly influenced the R(+)-7-OH-DPAT (10 and 100 microg/kg, s.c.)-induced amnesia. In addition, only a 1000 microg/kg dose of R(+)-7-OH-DPAT decreased locomotor activity; 1 and 100 microg/kg doses of the drug were ineffective. These results suggest that the amnesic effects of the dopamine D3 receptor agonist, R(+)-7-OH-DPAT, are not mediated via dopamine D1 or D2 receptors in the brain.

Animals↗
PubMed1997

Effects of the kappa-opioid dynorphin A(1-13) on learning and memory in mice.

The effects of intracerebroventricular administration of dynorphin A(1-13) on scopolamine- and pirenzepine-induced amnesia were investigated in mice by observing the step-down-type passive avoidance response and spontaneous alternation performance. The pre- or post-training, or preretention administration of dynorphin A(1-13) (0.3-10 micrograms) alone failed to affect the passive avoidance response, while scopolamine (1 mg/kg) significantly inhibited it. Dynorphin A(1-13) (1 microgram) given 15 min before training and retention tests, but not immediately after training, significantly improved the scopolamine (1 mg/kg)-induced impairment of passive avoidance response, indicating the anti-amnesic effects of dynorphin A(1-13). A lower dose (1 mg/kg) of the kappa-opioid receptor antagonist (-)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomorpha n reversed the anti-amnesic effects of dynorphin A(1-13) (1 microgram). In contrast, although dynorphin A(1-13) (1, 3 and 10 micrograms) did not influence spontaneous alternation performance, scopolamine (1 mg/kg) and the muscarinic M1 receptor antagonist pirenzepine (3 micrograms) markedly decreased spontaneous alternation performance. Dynorphin A(1-13) (3, 5.6 and/or 10 micrograms) significantly improved the scopolamine (1 mg/kg)- and pirenzepine (3 micrograms)-induced impairment of spontaneous alternation performance. The improving effects of dynorphin A(1-13) (3 micrograms) were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms), a kappa-selective opioid receptor antagonist. These results suggest that the stimulation of kappa-opioid receptors improves memory dysfunctions resulting from the blockade of muscarinic M1 receptors.

Analgesics, Opioid↗
PubMed1997

Effects of Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog, on elevated plus-maze learning and spontaneous alternation performance in mice.

1. The effects of intracerebroventricular administration of Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog, on plus-maze learning and spontaneous alternation performance were investigated in mice. 2. The pre- or posttraining or preretention administration of TAPA (0.3-3.0 ng) alone failed to affect transfer latency of plus-maze learning, whereas TAPA (3 ng) produced a significant decrease in percent alternation without affecting total arm entries. 3. beta-Funaltrexamine (5 micrograms) almost completely reversed the TAPA (3 ng)-induced decrease in percentage of alternation. 4. These results suggest that stimulation of mu-opioid receptors disrupts spontaneous alternation performance associated with spatial working memory.

Analgesics, Opioid↗
PubMed1997

Modulatory effects of morphine, U-50488H and 1,3-di-(2-tolyl)guanidine on cocaine-like discriminative stimulus in the rat using two-choice discrete-trial avoidance paradigm.

The present study was designed to investigate the effects of the mu-opioid morphine, trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]-benzene acetamide, methane sulfonate hydrate (U-50488H), a kappa-selective opioid receptor agonist, and 1,3-di-(2-tolyl)guanidine (DTG), sigma-receptor agonist, on the discriminative stimulus properties of cocaine in the rat trained to discriminate 10 mg/kg of cocaine from its vehicle in a shock avoidance paradigm. Morphine (1-5.6 mg/kg), U-50488H (1-10 mg/kg) or 1,3-di-(2-tolyl) guanidine (1 and 10 mg/kg) alone did not produce any stimulus effects in common with cocaine. In contrast, morphine (5.6 mg/kg) and DTG (10 mg/kg), unlike U-50488H (10 mg/kg), significantly shifted the stimulus-generalization curve for cocaine to the left. These results suggest that agonists for mu-opioid- and sigma-receptors augment the discriminative stimulus properties of cocaine.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Systemic administration of dynorphin A-(1-13) markedly improves cycloheximide-induced amnesia in mice.

The effects of systemic or intracerebroventricular injection of dynorphin A-(1-13), a kappa-selective opioid receptor agonist, on cycloheximide-induced amnesia were investigated by using a step-down-type passive avoidance task in mice. The intracerebroventricular injection of dynorphin A-(1-13) (0.3-3 micrograms) before training significantly prolonged step-down latency. The systemic administration of dynorphin A-(1-13) (1, 3 and/or 10 mg/kg, i.p.) before training or retention tests markedly inhibited the cycloheximide (30 mg/kg, s.c.)-induced shortening of step-down latency, indicating antiamnesic effects of dynorphin A-(1-13). One and 3 mg/kg doses of ((+/-)trans-3, 4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, methanesulfonate hydrate (U-50,488H), another kappa-selective opioid receptor agonist, significantly inhibited the shortening. The anti-amnesic effects of dynorphin A-(1-13) (3 and 10 mg/kg, i.p.) were almost completely antagonized by intracerebroventricular administration of the quaternary derivative of the opioid receptor antagonist naltrexone methobromide (0.3 microgram), but not by systemic administration of the opioid receptor antagonist (1 mg/kg, s.c.), demonstrating central mediation of the anti-amnesic effects of dynorphin A-(1-13). Furthermore, the kappa-selective opioid receptor antagonist, nor-binaltorphimine (2 mg/kg, s.c.), almost completely antagonized the effects of dynorphin A-(1-13) (3 and 10 mg/kg, i.p.). These results suggest that dynorphin A-(1-13) produces anti-amnesic effects through the blood-brain barrier.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Opioid receptor agonists selective for mu and kappa receptors attenuate methamphetamine-induced behavioral sensitization in the mouse.

The effects of intracerebroventricular (i.c.v.) injection of the mu-selective opioid receptor agonist [D-Ala2, N-MePhe4, Gly-ol]enkephalin (DAMGO) and the kappa-selective opioid receptor agonist dynorphin A-(1-13) on the development of methamphetamine-induced behavioral sensitization in the mouse were determined using multidimensional behavioral analyses based upon a capacitance system. Methamphetamine (2 mg/kg, s.c.) was administered to mice on 6 occasions at 3- or 4-d intervals. The methamphetamine-induced increase in linear locomotion and circling was markedly augmented by repeated administrations (3 or more times) of the drug, showing behavioral sensitization. Although repeated administrations of DAMGO (0.003 and 0.01 microgram, i.c.v.) or dynorphin A-(1-13) (3 and 12.5 micrograms, i.c.v.) alone did not produce any significant effects on behavior, repeated administrations of DAMGO (0.003 and 0.01 microgram, i.c.v.) and dynorphin A-(1-13) (3 and 12.5 micrograms, i.c.v.) attenuated the behavioral sensitization induced by methamphetamine (2 mg/kg, s.c.). The attenuating effects of DAMGO (0.003 and 0.01 microgram, i.c.v.) and dynorphin A-(1-13) (3 and 12.5 micrograms, i.c.v.) were fully reversed by withdrawal of these drugs for 3 weeks. Additionally, a single administration of DAMGO (0.003 and 0.01 microgram, i.c.v.) or dynorphin A-(1-13) (3 and 12.5 micrograms, i.c.v.) alone did not produce any significant effects on behavior; DAMGO (0.003 and 0.01 microgram, i.c.v.) and dynorphin A-(1-13) (3 and 12.5 micrograms, i.c.v.) only attenuated the behavioral sensitization which had previously been developed by methamphetamine (2 mg/kg,s.c.). These results suggest that opioid receptor agonists selective for mu and kappa receptors play an inhibitory role in the development of methamphetamine-induced behavioral sensitization.

Analgesics↗
PubMed1996

Neurokinin A and senktide attenuate scopolamine-induced impairment of spontaneous alternation performance in mice.

The effects of intracerebroventricular injections of the neurokinin-2 (NK-2) receptor agonist neurokinin A and the neurokinin-3 (NK-3) receptor agonist senktide on scopolamine (sc)-induced amnesia were investigated based on spontaneous alternation performance in mice. Spontaneous alternation performance is based on spatial working memory which produces a natural tendency to explore a less recently visited arm in a Y-maze. Neurokinin A (0.1-3 micrograms) or senktide (0.0003-0.03 microgram) alone did not influence either spontaneous alternation performance or total arm entries. However, neurokinin A (0.3 and 1 microgram) and senktide (0.003 and 0.03 microgram) inhibited the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting the scopolamine (1 mg/kg)-induced increase in total arm entries. Although the effects of neurokinin A (0.3 microgram) on the scopolamine-induced impairment of spontaneous alternation performance were almost completely antagonized by pretreatment with the NK-2 receptor antagonist cyclo (Gln-Trp-Phe-Gly-Leu-Met) (1 microgram), the inhibitory effects of senktide (0.003 microgram) were not influenced by pretreatment with the NK-3 receptor antagonist [Trp7, beta-Ala8]neurokinin A-(4-10). These findings suggest that neurokinin A inhibits the scopolamine-induced impairment of spontaneous alternation performance associated with working memory through the mediation of tachykinin NK-2 receptors, while senktide has some pharmacological action other than its effects on NK-3 receptors.

Amnesia↗
PubMed1995

Intrastriatal injection of opioid receptor agonists inhibits apomorphine-induced behavior in 6-hydroxydopamine-treated mice.

The effects of intrastriatal (i.st.) injections of mu-, delta-, and kappa-selective opioid receptor agonists on the augmentation of apomorphine-induced behaviors were determined in 6-hydroxydopamine-treated mice by using multidimensional behavioral analyses. 6-Hydroxydopamine (16 mu g/mu l, i.st.) was unilaterally injected into the striatum 30 min after pretreatment with desipramine (25 mg/kg, s.c). Mice were tested 14 days after injection of 6-hydroxydopamine. Apomorphine (0.5 mg/kg, s.c.) produced a marked increase in linear locomotion, contralateral circling and/or rearing behavior in 6-hydroxydopamine- but not vehicle-treated mice. Although the mu-selective opioid receptor agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAMGO) (0.1 and 0.3 ng, i.st.) or the kappa-selective opioid agonist dynorphin A-(1-13) (0.1 and 0.3 mu g, i.st.) did not produce any significant effects on behavior, these peptides had an inhibitory effect on the apomorphine (0.5 mg/kg, s.c.)-induced increase in behavioral responses such as linear locomotion, contralateral circling and/or rearing behavior in 6-hydroxydopamine-treated mice. The inhibitory effects of DAMGO (0.3 ng, i.st.) and dynorphin A-(1-13) (0.3 mu g, i.st.) were fully reversed by selective opioid receptor antagonists such as beta-funaltrexamine (5 mu g, i.c.v.) and (--)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomorph an (Mr2266) (10 mg/kg, s.c.), respectively. In contrast, the delta-selective opioid receptor agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.03, 0.1 or 0.3 mu g, i.st.) had no marked effects on the apomorphine (0.5 mg/kg, s.c.)-induced behavior in 6-hydroxydopamine-treated mice. These results suggest that the stimulation of mu- and kappa- but not delta-opioid receptors plays an inhibitory role in the behavioral augmentation induced by the activation of postsynaptic dopamine receptors in the striatum sensitized with 6-hydroxydopamine.

Animals↗
PubMed1995

Attenuation of memory with Tyr-D-Arg-Phe-beta-Ala-NH2, a novel dermorphin analog with high affinity for mu-opioid receptors.

The involvement of mu-opioid receptors in memory retrieval was examined in mice by using Tyr-D-Arg-Phe-beta-Ala-NH2 (TAPA), a novel dermorphin analog with high affinity for mu-opioid receptors, and passive avoidance learning. TAPA was intracerebroventricularly administered to mice before retention tests of passive avoidance learning. A 0.3-ng dose of TAPA markedly shortened step-down latency of passive avoidance learning, and the shortening of step-down latency was reversed by treatment with beta-funaltrexamine (5 micrograms), a mu-opioid receptor antagonist, indicating that TAPA (0.3 ng) attenuates memory retrieval. Although the attenuating dose (0.3 ng) of TAPA failed to affect horizontal or vertical locomotor activity, a 3-ng dose of TAPA showed a tendency to decrease vertical locomotor activity. A 30-ng dose of TAPA produced a significant increase in horizontal locomotor activity accompanied by a marked reduction of vertical locomotor activity. TAPA (3 ng) produced a significant increase in step-down latency of passive avoidance learning with lower intensity of electroshock or without electroshock during training. These results suggest that the activation of mu-opioid receptors impairs memory retrieval.

Amino Acid Sequence↗
PubMed1995

kappa-Opioid receptor agonists improve pirenzepine-induced disturbance of spontaneous alternation performance in the mouse.

We investigated the effects of kappa-opioid receptor agonists such as dynorphin A-(1-13) and U-50,488H on the muscarinic M1-selective receptor antagonist pirenzepine (3 micrograms, i.c.v.)-induced impairment of spontaneous alternation performance in the mouse. Although dynorphin A-(1-13)(1-5.6 micrograms, i.c.v.) or U-50,488H ((+/-)trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide, methanesulfonate hydrate) (0.1-1 mg/kg, i.p.) alone did not influence either spontaneous alternation performance or total arm entries, pirenzepine (3 micrograms, i.c.v.) impaired spontaneous alternation performance without producing any significant change in total arm entries. In contrast, dynorphin A-(1-13) (3 and 5.6 micrograms, i.c.v.) and U-50,488H (0.3 and 1 mg/kg, i.p.) ameliorated the pirenzepine (3 micrograms, i.c.v.)-induced impairment of spontaneous alternation performance. The ameliorating effects of dynorphin A-(1-13)(3 micrograms, i.c.v.) and U-50,488H (0.3 mg/kg, i.p.) were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms, i.c.v.), a kappa-opioid receptor antagonist. These results suggest that the stimulation of kappa-opioid receptors improves memory dysfunctions resulting from the blockade of muscarinic M1 receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1995

Substance P markedly ameliorates scopolamine-induced impairment of spontaneous alternation performance in the mouse.

We investigated the effects of intracerebroventricular injection of substance P (SP) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance in the mouse. SP (0.001-3 micrograms) alone did not influence either spontaneous alternation performance or total arm entries. Scopolamine (1 mg/kg) impaired spontaneous alternation performance accompanied by an increment in total arm entries. In contrast, SP (0.01-1 micrograms) significantly improved the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without influencing the scopolamine (1 mg/kg)-induced increase in total arm entries. The effects of SP (0.1 micrograms) on the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance were almost completely reversed by pretreatment with WIN 62577 (1 mg/kg), a tachykinin NK-1 receptor antagonist. These results suggest that SP improves the scopolamine-induced impairment of spontaneous alternation performance through the mediation of tachykinin NK-1 receptors.

Androstenes↗
PubMed1995

Improvement in exercise-induced left ventricular dysfunction by infusion of alpha-human atrial natriuretic peptide in coronary artery disease.

The effects of recombinant alpha-human atrial natriuretic peptide (alpha-hANP) infusion an acute left ventricular dysfunction provoked by exercise were examined in 14 men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was > 20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 microgram.kg-1.min-1). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p < 0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p < 0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Dynorphin A-(1-13) potently improves scopolamine-induced impairment of passive avoidance response in mice.

The effects of intracerebroventricular administration of dynorphin A-(1-13) on scopolamine-induced amnesia were investigated in mice by using a step-down type passive avoidance task. The pre- or post-training, or pre-retention administration of dynorphin A-(1-13)(0.3-10 micrograms) alone failed to affect step-down latency of the passive avoidance response, while scopolamine (1 mg/kg) significantly shortened step-down latency. Dynorphin A-(1-13)(1 microgram) given 15 min before training and retention tests but not immediately after training significantly improved the scopolamine (1 mg/kg)-induced shortening of step-down latency of the passive avoidance response, indicating antiamnesic effects of dynorphin A-(1-13) (1 microgram). A lower dose (1 mg/kg) of the kappa-opioid receptor antagonist, (-)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)- 2'-hydroxy-6,7-benzomorphan, reversed the anti-amnesic effects of dynorphin A-(1-13) (1 microgram). These results suggest that the antiamnesic effects of dynorphin A-(1-13) depend on the timing of drug treatments.

Amnesia↗
PubMed1995

Effects of centrally administered neuropeptides on discriminative stimulus properties of cocaine in the rat.

The present study was designed to investigate the effects of centrally administered neuropeptides on the discriminative stimulus properties of cocaine in the rat. Rats were trained to discriminate 10.0 mg/kg of cocaine from vehicle in a shock avoidance paradigm. The mu-selective opioid agonist [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.03-0.3 microgram, ICV) or the kappa-selective opioid agonist dynorphin A-(1-13) (1.0-10.0 micrograms, ICV) did not generalize to cocaine cue, although the delta-selective opioid agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (10.0 micrograms, ICV) reportedly generalizes to it through the mediation of delta-opioid receptors. Thyrotropin-releasing hormone (10.0-56.0 micrograms, ICV), somatostatin (0.3-3.0 micrograms, ICV), substance P (3.0-17.5 micrograms, ICV), or neurotensin (3.0-17.5 micrograms, ICV) did not produce any stimulus effects in common with cocaine. It appears that neuropeptides other than the delta-selective opioid do not play a major role in the discriminative stimulus properties of cocaine.

Animals↗
PubMed1995

Effects of galanin on passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice.

The present study was done to characterize the effects of intracerebroventricular injection of galanin (GAL) on memory processes by observing passive avoidance response, elevated plus-maze learning, and spontaneous alternation performance in mice. An intermediate dose (3 micrograms) of GAL (3 micrograms) significantly decreased step-down latency of passive avoidance response when given 15 min before training, whereas in particular the middle doses (0.3 and 1 microgram) of GAL significantly decreased it when given 15 min before retention tests. However, GAL (0.3-10 micrograms) was ineffective when given immediately after training. Physostigmine (0.2 mg/kg), a cholinesterase inhibitor, and oxotremorine (0.01 and 0.03 mg/kg), a cholinergic agonist, significantly inhibited the shortening of step-down latency induced by GAL (0.3 microgram) administered 15 min before retention tests, indicating the involvement of cholinergic dysfunction in the GAL (0.3 microgram)-induced shortening of step-down latency. In contrast, GAL (0.3-3 micrograms) failed to influence transfer latency in elevated plus-maze learning or percent alternation in spontaneous alternation performance. These results suggest that the activation of cholinergic neurons improves memory dysfunctions induced by GAL, which primarily impairs retrieval processes of memory. The lack of effects of GAL on the elevated plus-maze learning and spontaneous alternation performance may result from the selective effects of GAL in different learning paradigms.

Amino Acid Sequence↗