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Biomedical subjects

M Ukai

Publications and source records attributed to M Ukai.

At least 73 records · Page 4Linked to original sources
PubMed1993

DAMGO ([D-Ala2,NMePhe4,Gly-ol]enkephalin), but not DPLPE ([D-Pen2,L- Pen5]enkephalin), specifically inhibits methamphetamine-induced behavioral responses in the mouse.

The effects of intracerebroventricular (i.c.v.) injections of mu- and delta-selective opioid agonists on the methamphetamine-induced behavioral alterations in the mouse were determined by using multi-dimensional behavioral analyses. Methamphetamine (1.0 mg/kg) produced a marked increase in linear locomotion, circling, rearing and grooming behavior. Although the mu-selective opioid agonist [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.003 and 0.01 microgram) itself did not significantly affect different behavioral responses, DAMGO (0.003 and/or 0.01 microgram) antagonized the methamphetamine (1.0 mg/kg)-induced increase in behavioral responses such as linear locomotion, circling, rearing and grooming. Additionally, the effects of DAMGO (0.01 microgram) on the methamphetamine (1.0 mg/kg)-induced behavioral responses were fully reversed by pretreatment with the mu-selective alkylating agent beta-funaltrexamine (beta-FNA) (5.0 micrograms). In contrast, the delta-selective opioid agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.3 or 1.0 microgram) had no marked effects on the methamphetamine (1.0 mg/kg)-induced behavioral responses. These results suggest that the stimulation of mu but not delta opioid receptors plays an inhibitory role in the methamphetamine-induced behavioral responses.

Analgesics↗
PubMed1993

Discriminative stimulus properties of cocaine in the rat using a two-choice discrete-trial avoidance paradigm.

The discriminative stimulus effects of cocaine were studied in rats trained to discriminate 10.0 mg/kg cocaine from vehicle in a shock avoidance paradigm. Rats used could discriminate 10.0 mg/kg cocaine from vehicle within an average of 20 sessions after the start of discrimination training. Cocaine produced dose-dependent stimulus effects at 1.0- to 10.0-mg/kg doses. Cocaine (10.0 mg/kg) generalized to the dopamine reuptake inhibitor 1-[2-[bis(4-fluorophenyl)methyoxy]ethyl]-4-(3-phenylpropyl)piperaz ine 2HCl (GBR 12909) (30.0 mg/kg), methamphetamine (0.3 mg/kg), apomorphine (0.3 mg/kg), and the D2 dopamine agonist quinpirole (0.1 mg/kg), but not to the D1 dopamine agonist SK&F38393 (3.0-30.0 mg/kg). 1-Phenyl-2,3,4,5-tetrahydro-[1H]-3-benzazepine-7,8-diol HCl (SK&F38393) (10.0 mg/kg) combined with several doses (1.0-10.0 mg/kg) of cocaine shifted the stimulus generalization curve for cocaine to the left. Haloperidol (0.1 and 0.3 mg/kg), the D1 dopamine antagonist 7-chloro-2,3,4,5-tetrahydro-3-methyl-phenyl-1-H-benzazepine-7-ol maleate (SCH23390) (0.01-0.3 mg/kg), and the D2 dopamine antagonist S(-)-sulpiride (20.0 and 40.0 mg/kg) only partially blocked the stimulus effects of cocaine. Haloperidol (0.3 mg/kg) combined with SCH23390 (0.03 mg/kg) completely blocked the stimulus effects of cocaine. In addition, haloperidol (0.3 mg/kg) blocked the stimulus effects of quinpirole (0.1 mg/kg), in common with cocaine. These data suggest that both D1 and D2 dopamine receptors contribute to the discriminative stimulus effects of cocaine.

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

Receptor-selective opioid peptides fail to affect behavioral responses induced by a low dose of apomorphine in the mouse.

The effects of intracerebroventricular injections of the mu-selective opioid agonist DAMGO ([D-Ala2,NMePhe4,Gly-ol]enkephalin), the kappa-selective opioid agonist dynorphin A-(1-13), and the delta-selective opioid agonist DPLPE ([D-Pen2,L-Pen5]enkephalin) on the decrease in different behavioral responses induced by a low dose of apomorphine (0.03 mg/kg) were investigated in the mouse. A low dose (0.03 mg/kg) of apomorphine produced a marked decrease in behavioral responses such as circling and rearing. Although the dopamine D1 antagonist SCH 23390 (0.01 and 0.03 mg/kg) did not influence behavior induced by apomorphine (0.03 mg/kg), the dopamine D2 antagonist sulpiride (3.0 mg/kg) reversed the decrease in circling and rearing behavior induced by apomorphine, suggesting that the effects of apomorphine on circling and rearing are mediated through dopamine D2 autoreceptors. DAMGO (0.003 or 0.01 microgram), dynorphin A-(1-13) (3.0 or 10.0 micrograms), or DPLPE (0.3 and 1.0 microgram) had no significant effects on the apomorphine-induced decrease in circling and rearing behavior. These in vivo results suggest that opioid peptides selective for receptor types fail to influence drug effects mediated by dopamine D2 autoreceptors.

Analgesics↗
PubMed1993

Abnormal postexercise systolic blood pressure response is a good indicator of impaired left ventricular filling during supine cycle ergometer exercise in patients with coronary artery disease.

To determine whether the postexercise systolic blood pressure (SBP) response is a useful marker of left ventricular filling abnormalities, supine leg exercise testing was conducted in 14 control subjects and 70 patients with coronary artery disease (CAD). An abnormal postexercise SBP response (the ratio of SBP after 3 min of recovery to the peak exercise SBP) was defined as 0.85 or more, which represented the cutoff point with the highest sensitivity and specificity for prediction of pulmonary artery wedge pressure (PAWP) of at least 20 mmHg at peak exercise in CAD patients. There was a significant difference between the SBP ratios of the two groups (Control, 0.72 +/- 0.05; CAD, 0.86 +/- 0.13; p < 0.01). There was no significant difference between the PAWP of the two groups at rest, but the PAWP at peak exercise was significantly higher in the CAD group (20.2 +/- 8.9 mmHg) than in the control group (11.5 +/- 4.0 mmHg)(p < 0.01). PAWP at peak exercise was > or = 20 mmHg in 35 (50%) of the 70 CAD subjects. The SBP ratio was significantly correlated with PAWP at peak exercise (r = 0.67, p < 0.01) in the CAD group, but not in the control group. An SBP ratio of > or = 0.85 showed a sensitivity of 80% and a specificity of 80% for predicting a peak exercise PAWP of > or = 20 mmHg in CAD patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

[Opioid receptors in the brain related to behavior].

The effects of opioid peptides selective for opioid receptors on drinking, dopamine-related behavior, discriminative stimulus and memory processes were investigated in detail. Mu opioid receptors in the paraventricular nucleus of hypothalamus played an important role in drinking behavior. The stimulation of mu and kappa opioid receptors inhibited dopamine D2 receptor-related behavior. The discriminative stimulus effects of morphine and pentazocine were mediated through mu opioid receptors, while the stimulus effects of cocaine through delta opioid receptors. Mu opioid agonists elicited memory dysfunctions, whereas kappa opioid agonists such as dynorphin A-(1-13) improved amnesia induced by ischemia, basal forebrain-lesion or scopolamine. It appears that opioid receptors are fully involved in the neural basis of behavioral responses.

Animals↗
PubMed1992

Multidimensional behavioral analyses show dynorphin A-(1-13) modulation of methamphetamine-induced behaviors in mice.

The effects of intracerebroventricular (i.c.v.) injection of dynorphin A-(1-13) on methamphetamine-induced behavioral alterations in mice were determined by using multidimensional behavioral analyses. Methamphetamine (0.3, 1.0 and 3.0 mg/kg s.c.) produced a marked increase in linear locomotion, circling, rearing and/or grooming behaviors. The behavioral effects of methamphetamine (1.0 mg/kg s.c.) were almost completely antagonized by pretreatment with the dopamine D2 receptor antagonist, S(-)-sulpiride (3.0 and/or 10.0 mg/kg i.p.), but not with the dopamine D1 receptor antagonist, SCH 23390 (0.01 or 0.03 mg/kg i.p.). Although dynorphin A-(1-13) (3.0 or 12.5 micrograms i.c.v.) alone did not produce any significant effects on behavior, the methamphetamine (1.0 mg/kg s.c.)-induced increase in circling ipsilateral to the injection side was markedly enhanced by dynorphin A-(1-13) (12.5 micrograms i.c.v.). In contrast, the peptide (12.5 micrograms i.c.v.) inhibited the methamphetamine (1.0 mg/kg s.c.)-induced increase in rearing, whilst the increase in grooming remained unchanged. The effects of dynorphin A-(1-13) (12.5 micrograms i.c.v.) were fully reversed by the opioid antagonist, Mr 2266 (5.6 mg/kg s.c.). These results suggest that the unilateral administration (i.c.v.) of dynorphin A-(1-13) inhibits the activity of dopamine-elicited neurotransmission, resulting in an increase in ipsilateral circling and in a decrease in rearing.

Animals↗
PubMed1992

Combination of a delta opioid receptor agonist but not a mu opioid receptor agonist with the D1-selective dopamine receptor agonist SKF 38393 markedly potentiates different behaviors in mice.

The effects of intracerebroventricular injections of opioid peptides selective for mu or delta opioid receptors on behaviors induced by the D1 dopamine agonist SKF 38393 were investigated by using multi-dimensional behavioral analyses. A 10.0 mg/kg dose of SKF 38393 produced a marked increase in grooming behavior. The SKF 38393 (10.0 mg/kg)-induced increase in grooming behavior was clearly antagonized by SCH 23390 (0.03 mg/kg), a D1 dopamine antagonist, but not by S(-)-sulpiride (10.0 mg/kg), a D2 dopamine antagonist. [D-Ala2,MePhe4,Gly5-ol]enkephalin (DAMGO) (0.003 and 0.01 microgram), a mu-selective agonist, or [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.3 or 1.0 microgram), a delta-selective agonist, failed to affect spontaneous behaviors. The combination of DPLPE (0.3 and 1.0 microgram) but not of DAMGO (0.003 and 0.01 microgram) with SKF 38393 (10.0 mg/kg) produced a marked increase in linear locomotion and circuling away from the side receiving the peptide, whereas grooming behavior was not affected. The effects induced by DPLPE (1.0 microgram) plus SKF 38393 (10.0 mg/kg) were fully reversed by the delta-selective opioid antagonist naltrindole (10.0 mg/kg), SCH 23390 (0.03 mg/kg) and S(-)-sulpiride (10.0 mg/kg). These findings suggest that delta but not mu opioid systems interact with D1 dopamine receptors, resulting in a marked increase in linear locomotion and contralateral circuling without causing marked changes in grooming behavior.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Systemic administration of dynorphin A(1-13) markedly inhibits different behavioural responses induced by cocaine in the mouse.

The effects of systemic administration (i.p.) of dynorphin A(1-13) on the cocaine-induced behavioural alterations in the mouse were determined by using multi-dimensional behavioural analyses, based upon a capacitance system. A 1.0 mg/kg dose of cocaine did not influence behaviour, while increasing doses to 3-30 mg/kg produced a significant increment in the frequency of behaviour, such as linear locomotion, circling, rearing and grooming. Although a 1.0 mg/kg dose of dynorphin A(1-13) alone produced a significant decrease in grooming behaviour, larger doses (3.0 and 10.0 mg/kg) of the peptide failed to affect different behaviour. The cocaine (3.0 mg/kg)-induced increases in linear locomotion, circling and rearing behaviour were significantly inhibited by dynorphin A(1-13) (10.0 mg/kg). The inhibitory effects of dynorphin A(1-13) (10.0 mg/kg) were antagonized by the opioid antagonist Mr 2266 (5.6 mg/kg). It is thus possible that the systemic administration of dynorphin A(1-13) inhibits different behavioural responses induced by cocaine through the blood-brain barrier, although the instability of amino acid bonds or the relatively large molecular weight of dynorphin A(1-13), may result in the failure to demonstrate opioid activity by the peptide after systemic administration.

Analgesics↗
PubMed1992

Dynorphin A(1-13) preferentially inhibits behaviors induced by the D2 dopamine agonist RU 24213 but not by the D1 dopamine agonist SK&F 38393.

The effects of dynorphin A(1-13) on the D1 dopamine agonist SK&F 38393- and the D2 dopamine agonist RU 24213-induced behavioral alterations in the mouse were determined by using multidimensional behavioral analyses based upon a capacitance system. Although dynorphin A(1-13) (3.0 or 12.5 micrograms) alone did not produce any significant effects on behaviors, the peptide (12.5 micrograms) caused an inhibitory effect on the RU 24213 (3.0 mg/kg)-induced increase in behavioral patterns such as linear locomotion and circling except rearing and grooming behaviors. The antagonistic effects of dynorphin A(1-313) (12.5 micrograms) were fully reversed by the opioid antagonist M(r) 2266 (10.0 mg/kg). However, dynorphin A(1-13) (3.0 or 12.5 micrograms) failed to affect behaviors elicited by SK&F 38393 (10.0 mg/kg). These results suggest that dynorphin A(1-13) plays an inhibitory role in behaviors induced by the D2 dopamine agonist but not by the D1 dopamine agonist, possibly through the mediation of kappa-opioid receptors.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1992

Effects of [D-Ala2, D-Leu5]enkephalin and [D-Pen2, L-Pen5]enkephalin on apomorphine-induced motor activity in the mouse.

The effects of intracerebroventricular injections of opioid peptides such as DADL [( D-Ala2, D-Leu5]enkephalin) and DPLPE [( D-Pen2, L-Pen5]enkephalin) with different degrees of selectivity for delta- over mu-receptor on apomorphine (0.1, 0.3, 1.0 and/or 3.0 mg/kg)-induced motor activity were investigated in the mouse using multi-dimensional behavioral analyses. Lower doses (0.1 and 0.3 mg/kg) of apomorphine failed to affect significantly motor activity, whilst higher doses (1.0 and 3.0 mg/kg) of the drug produced a marked increase in linear locomotion, circling, rearing, and/or grooming behaviors. DADL (0.03, 0.1 or 0.3 microgram) by itself did not influence behaviors, while the peptide (0.1 and 0.3 microgram) produced a marked inhibition on apomorphine (1.0 but not 3.0 mg/kg)-induced increase in rearing behaviors. Furthermore, the inhibitory effect of DADL (0.3 micrograms) on the apomorphine (1.0 mg/kg)-induced increase in rearing was reversed by treatment with the alkylating agent beta-FNA (beta-funaltrexamine) (5.0 micrograms). In contrast to the effects of DADL, the much more delta-selective opioid agonist DPLPE (0.3, 1.0 or 1.75 micrograms) had no marked effects on apomorphine (1.0 mg/kg)-induced behaviors. These results suggest that delta opioid receptors do not play a principal role in the apomorphine-induced increase in circling, rearing or grooming behaviors.

Analgesics↗
PubMed1991

DAGO ([D-Ala2,N-Me-Phe4,Gly-ol]enkephalin) specifically reverses apomorphine-induced increase in rearing and grooming behaviors in the mouse.

The effects of intracerebroventricular injections (10 microliters) of the mu-selective opioid peptide DAGO on apomorphine (0.1, 0.56, 1.0 and/or 3.0 mg/kg)-induced motor activity were investigated in the mouse using multi-dimensional behavioral analyses. A lower dose (0.1 mg/kg) of apomorphine failed to significantly affect motor activity, whilst higher doses (0.56, 1.0 and 3.0 mg/kg) of the drug produced a marked increase in linear locomotion, circling, rearing and/or grooming behaviors. DAGO (0.003 and 0.01 micrograms) did not significantly affect different behaviors. DAGO (0.01 micrograms) antagonized the apomorphine (1.0 mg/kg)-induced increase in behaviors such as rearing and grooming. However, DAGO (0.003 or 0.01 micrograms) did not affect behaviors induced by a 3.0 mg/kg dose of apomorphine. Furthermore, the effects of DAG]O on apomorphine-induced behaviors were fully reversed by treatment with the mu-selective alkylating agent beta-FNA (beta-funaltrexamine) (5.0 micrograms). These results suggest that mu opioid receptors play a principal role in the apomorphine-induced increase in rearing and grooming behaviors.

Animals↗
PubMed1991

[D-Ala2,NMePhe4,Gly-ol5]enkephalin, but not [D-Pen2,L-Pen5]enkephalin, specifically inhibits behaviors induced by the dopamine D2 agonist RU 24213.

The effects of intracerebroventricular injection (10 microliters) of mu- and delta-selective opioid peptides on behaviors induced by the dopamine D2-selective agonist RU 24213 were investigated in the mouse, using multi-dimensional behavioral analyses. Fifteen to 30 min after the start of behavioral measurements, a 3.0 mg/kg dose of RU 24213 produced a marked increase in linear locomotion, circling, rearing and grooming behaviors. Although the mu-selective opioid peptide [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) (0.003 and 0.01 microgram) itself did not significantly affect behaviors, DAGO (0.01 microgram) antagonized the RU 24213 (3.0 mg/kg)-induced increase in behaviors such as linear locomotion, circling, rearing, and grooming. Additionally, the effects of DAGO on RU 24213-induced behaviors were fully reversed by treatment with the mu-selective alkylating agent beta-funaltrexamine (beta-FNA) (5.0 micrograms). In contrast, the delta-selective opioid peptide [D-Pen2,L-Pen5]enkephalin (0.3 or 1.0 micrograms) had no marked effects on RU 24213 (3.0 mg/kg)-induced behaviors. These results suggest that mu- but not delta-opioid receptors play an inhibitory role in the behaviors induced by the selective activation of dopamine D2 receptors.

Analysis of Variance↗
PubMed1991

Pentazocine-like discriminative stimulus effects of morphine are blocked by the dopamine D-1 antagonist SCH23390, but not by the dopamine D-2 antagonist sulpiride.

The effects of selective dopamine antagonists on the pentazocine-like discriminative stimulus effects of morphine were investigated in the rat trained to discriminate 3.0 mg/kg of pentazocine from vehicle. Morphine (3.0 mg/kg), a mu-selective agonist, produced stimulus effects in common with pentazocine (3.0 mg/kg), indicating that the stimulus effects are mediated through mu opioid receptors. The pentazocine-like stimulus effects of morphine (3.0 mg/kg) were clearly inhibited by the dopamine D-1 antagonist SCH23390 (0.03-0.56 mg/kg) but not by the dopamine D-2 antagonist sulpiride (20.0-80.0 mg/kg). The results suggest that the pentazocine-like discriminative stimulus effects of morphine are mediated via dopamine D-1 receptors.

Animals↗
PubMed1989

Dynorphin A(1-13) modulates apomorphine-induced behaviors using multidimensional behavioral analyses in the mouse.

The effects of intracerebroventricular injection of dynorphin A(1-13) on apomorphine-induced behavioral changes were investigated in the mouse using multidimensional behavioral analyses based upon a capacitance system. Although lower doses (0.1 or 0.3 mg/kg) of apomorphine were without marked effects on behaviors, a 0.56 mg/kg dose of the drug evoked a significant increase in rearing behaviors. Furthermore 1.0 and 3.0 mg/kg doses of apomorphine produced a marked increment in linear locomotion, circling and rearing. Dynorphin A(1-13) (3.0 or 10.0 microgram) itself had no effects on behaviors. The apomorphine (0.56 and 1.0 mg/kg)-induced increase in rearing behaviors was clearly inhibited by treatment with dynorphin A(1-13) (3.0 and 10.0 microgram). Simultaneously, the marked increases in linear locomotion and circling were displayed by apomorphine (1.0 mg/kg) plus dynorphin A(1-13) (10.0 microgram). The effects of dynorphin A(1-13) (10.0 microgram) on the apomorphine (1.0 mg/kg)-induced increase in rearing were entirely reversed by the opioid antagonist Mr2266. These results suggest that the antagonistic effects of dynorphin A(1-13) on the apomorphine (1.0 mg/kg)-induced increase in rearing are mediated via opioid receptors, possibly K-sites.

Animals↗
PubMed1989

Blockade of dopamine D1 receptors by SCH 23390 antagonizes discriminative stimulus effects of pentazocine.

The purpose of this investigation was to test the hypothesis that the discriminative stimulus properties of pentazocine are mediated through an interaction with dopamine receptors. Rats were trained to discriminate s.c. injections of pentazocine (3.0 mg/kg) from vehicle in a two-choice discrete trial avoidance paradigm. SCH 23390 (0.003-0.056 mg/kg), a selective antagonist of dopamine D1 receptors, inhibited the discriminative stimulus effects of pentazocine in a dose-dependent fashion, whilst the selective D2 receptor antagonist sulpiride (20.0-80.0 mg/kg) did not antagonize them. It appears that the dopamine D1 receptors play an important role in the discriminative stimulus effects of pentazocine.

Animals↗