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Biomedical subjects

S Ueki

Publications and source records attributed to S Ueki.

At least 109 records · Page 6Linked to original sources

The effect of kappa-opioid agonist U-50, 488H on wet-dog shaking behavior induced by hippocampal stimulation in rats.

The effect of a selective kappa-opioid agonist, U-50, 488H, on wet-dog shaking (WDS) induced by hippocampal stimulation was investigated and compared with that produced by morphine. U-50, 488H, as well as morphine, inhibited the appearance of WDS in a dose-dependent manner. U-50, 488H was approximately three times more potent than morphine in this effect. Neither drug showed any effect on hippocampal afterdischarge. The inhibition of WDS produced by U-50, 488H was blocked significantly by a kappa-opioid antagonist, MR-2266, but not by naloxone. On the other hand, the inhibitory effect of morphine was completely antagonized by both MR-2266 and naloxone. The present results strongly suggest that not only mu-but also kappa-opioid receptors are involved in the appearance of WDS induced by hippocampal stimulation.

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

Noradrenergic involvement in catalepsy induced by delta 9-tetrahydrocannabinol.

In order to elucidate the role of the catecholaminergic system in the cataleptogenic effect of delta 9-tetrahydrocannabinol (THC), the effect of pretreatment with 6-hydroxydopamine (6-OHDA) or with desipramine and 6-OHDA and lesions of the locus coeruleus were investigated in rats. The cataleptogenic effect of THC was significantly reduced in rats treated with 6-OHDA and in rats with lesions of the locus coeruleus but not in rats treated with desipramine and 6-OHDA, as compared with control rats. On the contrary, the cataleptogenic effect of haloperidol was significantly reduced in rats treated with desipramine and 6-OHDA but not in rats treated with 6-OHDA or in rats with lesions of the locus coeruleus. These results indicate that noradrenergic neurons have an important role in the manifestation of catalepsy induced by THC, whereas dopaminergic neurons are important in catalepsy induced by haloperidol.

Animals↗

The involvement of neuropeptide Y in the antimuricide action of noradrenaline injected into the medial amygdala of olfactory bulbectomized rats.

The present study was designed to clarify the functional role of neuropeptide Y (NPY) in the regulation of muricide induced by olfactory bulbectomy (OB) in relation to that of noradrenaline (NA) in the medial amygdala (AME). NA injected into AME inhibited muricide dose-dependently in OB rats. NPY at doses of 5 and 10 micrograms/microliter injected alone into AME failed to suppress muricide. When NPY 10 micrograms was injected into AME in combination with the maximal non-effective dose of NA, which was determined in each rat, muricide was suppressed in 80% of OB rats. The present study has provided the first evidence suggesting that NPY may be involved in the regulation of OB-induced muricide.

Aggression↗

The role of brain catecholamines in the exhibition of muricide induced by nucleus accumbens lesions and the effect of antidepressants in rats.

Changes in brain catecholamine content after lesioning the nucleus accumbens (ACC) and the effects of antidepressants were investigated using HPLC-ECD. ACC lesion reduced dopamine (DA) in the rostral caudate-putamen (r-CP), lateral hypothalamus (LH) and central amygdala (ACE). Imipramine (IMP) and nomifensine (NOM) increased DA in r-CP, caudal (c)-CP and basolateral amygdala. Mianserin (MIAN) and zimelidine (ZIM) increased DA only in c-CP. ACC lesion did not change DOPAC. Only IMP (in c-CP) and NOM (in r-CP and c-CP) increased DOPAC. Noradrenaline (NA) was decreased in c-CP and ACE after ACC lesion. IMP and ZIM displayed no effect on NA, while NOM increased NA in LH and frontal cortex (FC) and MIAN only in FC. These results suggest an important role for DA but not NA in the exhibition of muricide after ACC lesion, and in the antimuricide effect of antidepressants.

3,4-Dihydroxyphenylacetic Acid↗

Influences of electrical lesions of the dopaminergic system on morphine- and U-50,488H-induced analgesia in rats.

The effects of electrical lesions of brain areas containing dopamine cell bodies and terminals on morphine analgesia were investigated and compared with those of a selective kappa-opioid agonist, U-50,488H. The analgesic effect of morphine 10 mg/kg IP was potentiated significantly in substantia nigra (SN)- or caudate-putamen-lesioned rats, but not by ventral tegmental area (VTA) or nucleus accumbens lesions. However, electrical lesions of neither SN nor VTA affected the analgesic activity of U-50,488H 32 mg/kg IP. Although the tolerance to morphine analgesia developed in all four of the lesioned groups as well as in sham-lesioned rats, a significant analgesic effect in the SN-lesioned group prevailed during chronic treatment for 14 days as compared with that of sham-lesioned rats. From these results, it is suggested that morphine analgesia is potentiated by dysfunction of the nigro-striatal dopaminergic system, but not by that of the mesolimbic dopaminergic system, the central dopaminergic system is not involved in the appearance of U-50,488H analgesia and is not basically related to the development of tolerance to morphine analgesia.

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

A new method for screening anxiolytic drugs in rats.

In order to evaluate the anxiolytic action of drugs, a simple experimental procedure using a corridor-type runway was designed. In this apparatus, five food pellets were set in a row on a plastic platform. Rats with one day food-deprivation take a food pellet and then usually return to the start box. The time required to take 5 pellets (total time) and the number of returns were recorded. Diazepam (DZP) at 1-3.2 mg/kg and zopiclone (ZOP) at 10 mg/kg caused decreases in both parameters. These effects were blocked by the benzodiazepine receptor blocker, Ro15-1788, at 10 mg/kg. However, tracazolate failed to produce any change in both parameters. Haloperidol and imipramine prolonged the total time while reducing the number of returns. In contrast to DZP and ZOP, pentetrazol, well known to possess an anxiogenic effect, prolonged the total time. These results suggest that decreases in both the total time and the number of returns produced by DZP and ZOP may be related to their anxiolytic action which is mediated by a benzodiazepine receptor. Therefore, this procedure would be a simple and selective method for detecting benzodiazepine-type anxiolytics.

Animals↗

Changes of brain monoamine contents in three models of experimentally induced muricide in rats.

Monoamine levels were measured by high performance liquid chromatography with electrochemical detection in seven brain regions of three models of experimentally-induced muricide (mouse-killing behavior) in rats (bilateral olfactory bulbectomized rats: OB rats, midbrain raphe nuclei lesioned rats: Raphe rats and nucleus accumbens lesioned rats: Acc rats). Noradrenaline (NA) levels in the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), 3,4-dihydroxyphenylacetic acid (DOPAC) levels in LH and homovanillic acid (HVA) levels in the frontal cortex (FC) were increased in all three muricide models. In LH, serotonin (5-HT) levels increased in Acc rats and the 5-hydroxyindoleacetic acid (5-HIAA)/5-HT ratio was reduced in OB rats. But in VMH an increase in NA level was not accompanied by any changes of other amines in three muricide models except for 5-HT and 5-HIAA in Raphe rats. In the mamillary body (MB), NA level was increased and 5-HIAA/5-HT ratio was decreased in both OB and Acc rats. Monoamine changes in the amygdaloid nuclei were different in three muricide models, suggesting that the role of monoamines in various nuclei of the amygdala may be different in each muricide model. The present findings suggest that both noradrenergic (LH and VMH) and serotonergic function (LH and MB) may play an important role in exhibiting muricide of OB, Raphe and Acc rats, while dopaminergic function (LH and FC) may be related rather to hyperirritability elicited in these three muricide models.

3,4-Dihydroxyphenylacetic Acid↗

Behavioral pharmacology of zopiclone.

The pharmacological properties of zopiclone, a cyclopyrrolone derivative, have been studied in comparison with diazepam, nitrazepam, and flurazepam, on behavioral tests in mice and rats, including open-field activity, Skinner box conflict test, hyperemotionality and muricidal behavior of olfactory bulbectomized or raphectomized rats, pentetrazol or electroshock convulsions, inclined screen, rotarod, and thiopental-, ether-, or ethanol-induced anesthesia. Zopiclone exhibited pharmacological properties qualitatively similar to those of benzodiazepines especially in conflict, aggressivity, and pentetrazol-induced convulsion tests. On the other hand, its myorelaxant activity was somewhat weaker than that of the reference drugs. The pharmacological effects of zopiclone were of short duration.

Aggression↗

A new forced swimming test for the evaluation of antidepressants in rats by recording vibration of a water tank.

In order to more objectively evaluate drug effects in the forced swimming test proposed by Porsolt et al. as a screening method for antidepressants, vibrations of the wall of a tank caused by rats trying to escape from water were recorded. Locomotor activity was also measured in an activity cage. Male Wistar rats were forced to swim once daily for 15 min in a tank of 25 degrees C water filled to a depth of 20 cm. After 4 d sessions of swimming, drugs were administered i.p. 3 times (24, 5 and 1 h prior to the test session). On day 5, 45 min after the last injection of a test drug, locomotor activity was measured for 15 min and then the rat was subjected to the forced swimming test. All antidepressants tested, dose-dependently increased tank vibration. Nomifensine, atropine, methamphetamine, chlorpheniramine and diazepam increased locomotor activity. The remaining drugs had no effect or reduced locomotion. In addition, the pattern of the tank vibrations, caused by rats treated with most drugs, like atropine, showed a burst during the first 5 min followed by sporadic vibrations. Nomifensine and methamphetamine, on the other hand, caused vibrations throughout the 15 min test session. A specific effect of antidepressants was revealed by this forced swimming test in combination with the measurement of locomotor activity.

Animals↗

[Electroencephalographic effect of quinupramine in the rabbit].

Electroencephalographic (EEG) effect of quinupramine was investigated in unanesthetized rabbits with chronic electrode implants, and it was compared with those of imipramine and amitriptyline. Quinupramine (0.56-3.2 mg/kg) induced a marked drowsy pattern of spontaneous EEG: high voltage slow waves increased in the cortex, while the hippocampal theta rhythm was desynchronized. Imipramine (1.0-5.6 mg/kg) and amitriptyline (0.56-3.2 mg/kg) also elicited similar EEG effects. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus was markedly suppressed by quinupramine, imipramine and amitriptyline. The EEG arousal response induced by i.v. injection of physostigmine was markedly suppressed by quinupramine, amitriptyline and imipramine. Quinupramine showed no significant effect on the photic driving response and recruiting response. Quinupramine slightly enhanced the limbic afterdischarges elicited by either hippocampal or amygdaloid stimulation, while amitriptyline and imipramine caused an initial suppression followed by a quick recovery. The EEG effects of quinupramine were similar to those of amitriptyline in both qualitative and quantitative aspects.

Amitriptyline↗

Rolipram as a discriminative stimuli: transfer to phosphodiesterase inhibitors.

Rats were trained to discriminate (+/-)-rolipram (0.32 mg/kg, i.p.) from saline in a two-lever food-reinforced drug discrimination procedure (FR 10). (+/-)-Rolipram served as a drug discriminative stimulus, and its discrimination was readily established with a mean of 42 training sessions to achieve criterion performance (at least 80% correct response in the consecutive generalization tests with both saline and (+/-)-rolipram). Thereafter, this stimulus was stably maintained. The (-)-isomer of rolipram was generalized at about one-third of the training dose of the (+/-)-compound, but the (+)-isomer was generalized only at 10 times the dose of the (+/-)-compound. This finding suggests that the (-)-compound is more extensively involved as a stimulus than either (+/-)-rolipram or the (+)-isomer. Ro20-1724, caffeine and theophylline, which are phosphodiesterase inhibitors, were generalized to (+/-)-rolipram. This result strongly suggests that phosphodiesterase inhibition may be an important factor involved in (+/-)-rolipram discrimination.

Animals↗

Behavioral and electroencephalographic effects of zopiclone, a cyclopyrrolone derivative.

Behavioral effects of zopiclone were investigated in mice and rats and compared with the data on diazepam, nitrazepam and flurazepam. The electroencephalographic effect of the drug was also examined in unanesthetized rabbits with chronic electrode implants and compared with that of diazepam. The present results indicate that zopiclone possesses pharmacological properties qualitatively similar to benzodiazepines, which are characterized by potent anticonflict and antiaggressive effects and much weaker anticonvulsant, muscle relaxant, ataxiogenic, sedative and anesthesia potentiating effects; the properties of this drug were compared with those of diazepam, nitrazepam and flurazepam. Zopiclone suppressed the EEG arousal responses and inhibited afterdischarges induced by electrical stimulation of the hippocampus and amygdala. The effects of zopiclone on EEG and afterdischarges were approximately 1/10 those of diazepam.

5-Hydroxytryptophan↗

Effects of dibutyryl cyclic adenosine monophosphate and dibutyryl cyclic guanosine monophosphate on neuron activity of suprachiasmatic nucleus in rat hypothalamic slice preparation.

In order to elucidate the role of cyclic nucleotides in the suprachiasmatic nucleus, we examined the effect of dibutyryl cyclic AMP (c-AMP) and dibutyryl cyclic GMP (c-GMP) on single neuronal activity of the suprachiasmatic nucleus of the rat. A hypothalamic slice about 300 micron thick, including the suprachiasmatic nucleus, was cut coronally using a vibratome. By means of bath- as well as iontophoretic application, c-AMP and c-GMP caused mainly an inhibition and facilitation in suprachiasmatic neuronal activity, respectively. The present results suggest that c-AMP and c-GMP play an important role in regulation of suprachiasmatic neuronal activity as a second messenger and that these two nucleotides may function as a reciprocal messenger.

Animals↗

An important role of the central amygdaloid nucleus and mammillary body in the mediation of conflict behavior in rats.

The present study was designed to elucidate the functional role of central amygdaloid nucleus (ACE) and mammillary body (MB) in the mediation of behavioral suppression using rat conflict punishment procedure. Lesion of ACE produced a significant and long-lasting increase in the punished responding during the experimental period. Rats with lesion of MB also showed a significant increase in the punished response 10-14 days after brain lesioning. These results demonstrated the important role of ACE and MB in the mediation of behavioral suppression such as conflict behavior.

Amygdala↗

Importance of gastric motility in the pathogenesis of indomethacin-induced gastric lesions in rats.

Effects of indomethacin on gastric motility and secretion, and levels of endogenous prostaglandins (PGs) were investigated in rats, in attempts to elucidate the factors involved in the pathogenesis of indomethacin-induced macroscopic gastric lesions. Subcutaneous administration of indomethacin had no effect on the gastric mucosa at doses of 1 and 5 mg/kg, but induced visible lesions dose dependently at over 10 mg/kg within 4 hr. At 25 mg/kg, there were apparent nonhemorrhagic lesions within 1 hr, and these lesions became hemorrhagic with time. Acid secretion was not affected by this agent at either dose level, but pepsin or acid-induced HCO3- secretion was significantly increased or decreased, respectively, at a dose less than 5 mg/kg, which did not induce any lesion. Gastric motility, however, was dose dependently increased after administration of indomethacin, and its effect was significant at 10 mg/kg or greater. Time-course changes in the motility were in parallel with those of the lesion formation. PGE2 and 6-keto PGF1 alpha levels in the corpus mucosa were reduced around 80-90% for more than 4 hr from 30 min after administration of 5 mg/kg or more of indomethacin. When all the above changes caused by indomethacin were plotted for the various doses, a significant correlation (r = 0.958, P less than 0.01) was found between the lesion index and the changes in motility, but not in other factors, including PG levels. These results indicate that gastric motility may be an important factor in the pathogenetic mechanism of indomethacin-induced gastric lesions in rats. A deficiency of endogenous PGs may be a prerequisite for later extension of the lesions.

6-Ketoprostaglandin F1 alpha↗

Effect of monoamines on field potentials in the suprachiasmatic nucleus of slices of hypothalamus of the rat evoked by stimulation of the optic nerve.

The effects of the application of serotonin, histamine, noradrenaline and dopamine to the bath on field potentials in the suprachiasmatic nucleus evoked by stimulation of the optic nerve were studied using a hypothalamic slice. Stimulation of the contralateral optic nerve evoked fast positive and late large negative waves in the suprachiasmatic nucleus. The monoamines produced a dose dependent suppression of the amplitude of the negative wave but did not affect that of the positive waves, and the order of potency was serotonin greater than noradrenaline greater than dopamine greater than or equal to histamine. The negative wave was suppressed by phenylephrine (0.1-10 microM) in a dose-dependent manner, whereas it was unaffected by isoproterenol (0.1-10 microM). The suppression of the negative wave produced by the application of histamine and noradrenaline was antagonized by the H1-receptor antagonist, diphenhydramine and the alpha 1-receptor antagonists, phenoxybenzamine and phentolamine. Therefore, the suppression of the negative wave by histamine and noradrenaline was mediated by the H1-receptor and alpha 1-receptor, respectively. The present study indicates that monoamines may play an inhibitory role in the regulation of neurotransmission in the retinohypothalamic pathway to the suprachiasmatic nucleus.

Animals↗

Influence of excitatory amino acid receptor antagonists and of baclofen on synaptic transmission in the optic nerve to the suprachiasmatic nucleus in slices of rat hypothalamus.

Electrical stimulation of the optic nerve evoked two positive waves with short latency, followed by a large negative wave in the suprachiasmatic nucleus of slices of hypothalamus of the rat. The latency to peak of the two positive waves and the large negative wave were 2.7 +/- 0.1, 6.1 +/- 0.1 and 10.3 +/- 0.5 msec, respectively. Only the large negative wave disappeared in low calcium Ca2+-high magnesium (Mg2+) Krebs solution and with the addition of tetrodotoxin (1 microM) all the waves disappeared. Baclofen inhibited the large negative wave in a dose-dependent manner but not the two positive waves. Excitatory amino acid antagonists also inhibited only the large negative wave, i.e. it was reduced to about 70% by 1 mM glutamic acid diethyl ester and to about 50% by both 1 mM 2-amino-4-phosphonobutyric acid and 1 mM DL-2-amino adipic acid. All waves were unaffected by 0.1 mM atropine, hexamethonium and curare. These results indicate that two positive waves, induced by stimulation of the optic nerve are attributed to nerve conduction and the large negative wave to the neurons of the suprachiasmatic nucleus, and that the neuronal pathway from the optic nerve to the suprachiasmatic nucleus may include aspartate and/or glutamate as an excitatory neurotransmitter.

Acetylcholine↗