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J Yanai

Publications and source records attributed to J Yanai.

At least 73 records · Page 4Linked to original sources
PubMed1985

Implications of dopamine agonist-induced hypothermia following increased density of dopamine receptors in the mouse.

An investigation was made of hypothermia induced by dopamine (DA) agonists as a model of the effect of various treatments or conditions on the sensitivity of central postsynaptic DA receptors. Selective supersensitivity of these receptors (defined as an increase in Bmax) was induced by means of intraventricular injections of 6-hydroxydopamine (6-OHDA) in animals pretreated with desmethylimipramine (DMI). Supersensitivity was also produced by the chronic administration of haloperidol. The supersensitivity of DA receptors induced by 6-OHDA was found to be associated with a reduced hypothermic response to apomorphine. Supersensitivity elicited by the chronic administration of haloperidol, which very probably did not produce a specific effect on the density of DA receptors but also affected serotonergic receptors, did not elicit any change in hypothermia induced by apomorphine. The results of the present study are not consistent with the view that DA receptors mediate hypothermia per se, but rather suggest that hypothermia induced by DA agonists is more complex, probably involving serotonergic receptors primarily, though other factors may also be contributory. Furthermore, the results of the present study suggest that the functional significance of supersensitivity of DA receptors induced by 6-OHDA versus chronic treatment with haloperidol may be quite different, depending upon the effector system examined.

Animals↗
PubMed1985

Studies on brain monoamine neurotransmitters in mice after prenatal exposure to barbiturate.

Pregnant HS/Ibg mice received 3 g/kg phenobarbital in their milled food; control dams received unadulterated milled food. Their offspring were tested on ages 22 and 50 days for norepinephrine (NE) and dopamine (DA) levels and DA turnover in the hypothalamus and striatum. Additional groups were tested on days 8, 22, and 50 for brain stem tryptophan hydroxylase (TPH) activity. Hypothalamic DA level among offspring with prenatal PhB exposure (B offspring) was 37% below control level on age 22 days and 61% below control on day 50 (p less than 0.001). Hypothalamic NE level of B offspring was reduced on age 50 days (52%, p less than 0.05) and not on day 22. DOPAC level and DA turnover did not differ among B and control groups. Prenatal exposure to PhB did not have a significant effect on TPH activity. The changes in catecholamines may mediate, at least in part, some of the early barbiturate induced neuromorphological and behavioral changes previously found in our laboratory.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1985

Early phenobarbital-induced alterations in hippocampal acetylcholinesterase activity and behavior.

Early exposure to phenobarbital (PhB) causes marked destruction of large neurons which are then forming both in the hippocampus and in the cerebellum. Such exposure to PhB also reduces the achievements of mice in hippocampus-related behaviors such as radial 8-arm maze performance. Experimental evidence suggests that these behaviors are partially mediated by cholinergic transmission. We studied the performance of mice, exposed to PhB prenatally or neonatally, in radial 8-arm maze. Both treatments caused significant impairments in the animals' performance in the maze. Acetylcholinesterase (AChE) and pseudocholinesterase (pChE) activities were studied in the hippocampus and cerebellum of mice who were exposed to PhB prenatally or neonatally. These enzymes are involved both in cholinergic transmission and in neuronal development. A significant decrease (13-16%, P less than 0.01) in hippocampal AChE specific activity was found between days 15 and 22 in animals exposed to PhB neonatally. The total hippocampal activity of AChE was also greatly reduced (25-39%, P less than 0.01) during that period as a result of both the reduction in specific activity and a reduction in hippocampal weight of the treated animals. These alterations were transient and were not detected in adulthood. No changes in hippocampal AChE or pChE activities were found in animals treated prenatally. Cerebellar AChE and pChE activities were not altered after prenatal nor after neonatal exposure to PhB. It is possible that the short-term effect of neonatal treatment on AChE specific activity might mediate the long-term impairments in hippocampus-related behaviors.

Acetylcholinesterase↗
PubMed1985

Comparison of the effects of barbiturate and ethanol given to neonates on the cerebellar morphology.

Previous studies from different laboratories have suggested that neonatal exposure to barbiturate and ethanol induces long-term changes in cerebellar morphology. The present study was designed to compare in similar conditions the effect of neonatal exposure to maximal doses of barbiturate or ethanol on cerebellar morphology. Phenobarbital was administered via daily injections of 50 mg/kg on neonatal days 2-21 (B group). Ethanol was similarly administered in doses of 3 g/kg (E3g) and the submaximal dose of 2 g/kg (E2g). At age 50 days, the cerebella of treated and control offspring were subjected to histological analysis. The sagittal areas of the cerebellar layers were similarly reduced compared to controls in both B and E3g groups. In addition, B and E3g groups exhibited a similar deficit in the number of the cerebellar Purkinje and granule neurons. As barbiturate and E3g, a submaximal dose of ethanol (B2g) induced a deficit in the number of cerebellar Purkinje cells. However, it did not affect the granule cells and the area of the cerebellar layers. The results suggest that under standardized conditions, barbiturate and ethanol have a similar potent neurotoxic effect on the cerebellum. That is, they both impair the development of the cerebellar layers to a similar extent and destroy neurons even after they have already formed.

Animals↗
PubMed1985

Prenatal versus neonatal long-term effect of phenobarbital on mouse microsomal drug-oxidizing system.

Mice were exposed to phenobarbital (PhB) prenatally or neonatally. Prenatal treatment (PreB) was accomplished by feeding the mother PhB, 3 g/kg milled food on gestation days 9-18. Neonates (NeoB mice) were injected daily with 50 mg/kg PhB. The activity of the hepatic microsomal drug-oxidizing system was assayed in the PreB mice (at ages 28 and 50 days), NeoB mice (22, 28 and 50 days) and controls. PreB had at day 28 only small increases in enzyme activity. However, on day 50 there was a 3-fold increase in PhB level compared to control. Among NeoB mice the enzyme activity was 3 times above control on day 22 but the increase was abolished on days 28 and 50. Thus, the long-term increase in the microsomal drug-oxidizing system takes place only after prenatal (and not neonatal) PhB exposure, and the increased enzyme activity occurs around maturity.

Animals↗
PubMed1984

Effect of naloxone on dopamine uptake and release in vitro in the striatum.

The opiate antagonist naloxone (NX) can inhibit the stereotyped behavior elicited by the directly acting dopamine (DA) agonist apomorphine, while potentiating the same behavior induced by amphetamine, an indirect DA agonist. Since NX does not appear to bind to striatal 3H-DA receptors, these effects may be mediated by an indirect action exerted by naloxone on the nigrostriatal pathway. To confirm this, the effect of NX on DA uptake in striatal homogenates was assessed in vitro, and also the effect of NX on DA release in both striatal synaptosomes and slices. While NX had no effect on its own in either of these preparations, it was able to significantly enhance the release of DA induced by d-amphetamine. Since NX has no effect by itself on either behavior or DA release, it appears that NX can exert an active effect on the release of striatal DA only if the nigrostriatal pathway is in a state of arousal (e.g. by amphetamine).

Animals↗
PubMed1984

The role of dopaminergic mechanisms in mediating the central behavioral effects of morphine in rodents.

Morphine has been universally assumed to act solely on opiate receptors, and predominantly on mu receptors. In consonance with this, several studies have demonstrated that opiate mu agonists and dopaminergic agonists and antagonists are incapable of binding each other's receptors, except at extremely high concentrations (nor, for that matter, are acetylcholine, serotonin, gamma-hydroxybutyrate, norepinephrine or histamine able to bind opiate receptors). Yet, while other neurotransmitter antagonists (e.g. alpha- and beta-adrenoceptor-blocking agents) are for the most part limited in their effect on opiate-induced responses, many of the central effects elicited by morphine and other opioids have been found to be markedly potentiated by dopamine (DA) antagonists and reversed by direct and indirect DA agonists. Even more significantly, DA antagonists (especially those appreciably inhibiting DA release selectively) can also mimic many of these effects in low to moderate doses. Since DA antagonists do not act by binding opiate receptors, it is quite likely that morphine and other opiate mu receptor agonists may at least partially induce many of their acute central effects by means of an inhibition of postsynaptic DA receptor arousal. This appears to be a consequence of morphine binding its own (mu) receptors localized on central DA nerve terminals, resulting in an alteration of presynaptic DA release. This review does not exclude the important role of other neurotransmitter substances in the action of morphine, but rather emphasizes, and limits itself to considering, the importance of the role of dopamine in morphine-induced behaviors.

Aggression↗
PubMed1984

Ascorbic acid effect on ethanol sensitivity via possible dopaminergic mediation.

Mice were injected with 0, 107, 215, 430, or 1720 mg/kg of ascorbic acid. Thirty min later they were tested for ethanol (3.5 g/kg) induced sleep time. Brain ethanol levels were determined upon awakening. Another group of mice were tested for apomorphine (3 mg/kg) induced locomotor activity also 30 min after ascorbic acid injection. Ascorbic acid in doses above 215 mg/kg augmented ethanol sleep time up to 210% at the highest doses, the increase being significant from 430 mg/kg. Brain ethanol levels upon awakening were reduced by ascorbic acid treatment; this reduction was significant at 1720 mg/kg dose. Ascorbic acid decreased apomorphine-induced locomotor activity in a dose response manner that paralleled the ascorbic acid increase of ethanol sleep time. At the highest dose of ascorbic acid, apomorphine-induced locomotor activity was completely eliminated. It is suggested that ascorbic acid increases brain sensitivity to ethanol by lowering the activity of dopamine receptors.

Animals↗
PubMed1983

Isolation reduces midbrain tryptophan hydroxylase activity in mice.

Male C57 mice were divided into two experimental groups: "Isolated" and "Grouped". Isolated mice were housed individually for 30 or 45 days; Grouped mice were housed five per cage. Midbrain tryptophan hydroxylase activity was determined at the end of the isolation period. Isolated mice showed 35% less tryptophan hydroxylase activity than grouped mice (P less than 0.001). Prolongation of the isolation (45 vs 30 days) did not further reduce the enzyme activity. The changes in tryptophan hydroxylase activity may be related to behavioral changes induced by isolation.

Animals↗
PubMed1983

The comparative roles of dopaminergic and serotonergic mechanisms in mediating quipazine induced increases in locomotor activity.

The effect of dopaminergic and serotonergic agonists and antagonists on quipazine induced locomotor activity was investigated in rats. Though quipazine is generally considered to be a relatively pure serotonergic agonist, its effects on locomotor activity were inhibited by small doses of a centrally acting DA receptor blocking agent (haloperidol), while three different serotonergic (5-HT) antagonists were without effect on this behavior. Moreover, quipazine induced locomotor activity was markedly inhibited by the 5-HT substrate 5-hydroxytryptophan. The data suggest that quipazine induced locomotor activity primarily involves dopaminergic mechanisms, with 5-HT playing either no role in stimulating this behavior, or a subsidiary one, requiring intact central dopaminergic receptors for its expression.

Animals↗
PubMed1983

Acceleration of wound healing by topical application of honey. An animal model.

Commercial unboiled honey was applied topically to open wounds of 12 mice. Twelve other mice served as a control group and their wounds were dressed with saline solution only. Wound healing was judged histopathologically by measuring the thickness of granulation tissue, epithelization from the periphery of the wound, and the size of the open wounds. The animals were killed 3, 6, and 9 days from the day they were wounded and treated, and their wounds were examined histopathologically. According to the three mentioned criteria, wounds of the honey-treated animals healed much faster than the wounds of the control animals (p less than 0.001). Unboiled commercial honey seems to accelerate wound healing when applied topically due to its energy-producing properties, its hygroscopic effect on the wound, and its bacteriocidic properties. Our results suggest that honey applied topically on open wounds accelerates the healing process.

Administration, Topical↗
PubMed1983

Ultrastructural evidence of long-lasting cerebellar degeneration after early exposure to phenobarbital in mice.

Previous studies in this laboratory demonstrated a 20 to 30% reduction in cerebellar Purkinje and granule cells after exposure to phenobarbital (PhB) early in life. Therefore, neurons in the cerebellar cortex were examined for signs of cytologic degeneration using transmission electron microscopy (TEM) after exposure to PhB pre- and postnatally. Pregnant mice were given the acid form of PhB in their milled food (3 g/kg, gestation days 9 to 18) and water, ad libitum. Neonates were injected s.c. with an aqueous solution of sodium PhB (50 mg/kg body weight), days 2 to 21 after delivery. Controls were fed regular food or injected with the vehicle. The offspring were anesthetized on day 14 or 50 by an acute overdose of PhB and immediately perfused with a formaldehyde-paraformaldehyde or glutaraldehyde solution. The pyramis vermis of the cerebellar cortex was excised and processed routinely for TEM. The three layers of the cortex were examined. A short-term effect (at day 14) was found. More significantly, the treatment appeared to establish or trigger a degenerative process, the results of which were still apparent at day 50, more than 30 days after the termination of PhB treatment. Using double-blind evaluation for the presence and frequency of abnormalities, the cerebellar neurons of treated animals had 155 to 300% more abnormalities compared with control animals. Abnormalities included (i) Mitochondrial degeneration, ranging from swelling, collapse of cristae, vacuolization, to total granularization; (ii) lamellar bodies distributed throughout the cytoplasm and in cell processes; and (iii) myelin sheath degeneration, including periodic swelling and collapse, twisting of the coat, and scattered, unevenly stained areas. Damage was usually focal. Affected cells were found adjacent to normal cells in all areas of the cortex. PhB may cause the neural damage through a possible hormonal role.

Animals↗
PubMed1983

Effect of phenobarbital on in vitro aromatization of testosterone to estradiol by adult male mice brain.

Adult male mice were given phenobarbital (PB) through their food containing 3.5 g/kg for 5 consecutive days. On days 3 and 5 of treatment and 5 days following termination of PB treatment the animals were sacrificed and the in vitro conversion of (1,2-3H)-testosterone to estradiol in the brains was measured. During PB treatment brain aromatization of testosterone was reduced by approximately 50% as compared to the untreated group. Five days after termination of PB administration, brain aromatase activity was as in the control group. Direct addition of PB to brain homogenates (200 micrograms/ml) reduced the conversion of testosterone to estradiol by approximately 30%. These results demonstrate that PB can act directly upon brain tissue to inhibit aromatase activity. It is assumed that this effect of PB is one of the mechanisms by which this drug inhibits testosterone action.

Animals↗
PubMed1983

Effect of naloxone and morphine on dopamine agonist-induced stereotypy in rats and guinea pigs.

Naloxone (0.80 mg/kg) and morphine (7.5 mg/kg) were given to rats or guinea pigs with increasing doses of amphetamine (0.5-6.0 mg/kg) to determine their respective effects on amphetamine-induced stereotypy. In contrast to the inhibiting and potentiating effect of these agents on apomorphine-induced stereotyped behavior, naloxone enhanced and morphine markedly attenuated amphetamine-induced stereotypy. Since other investigators have reported that drugs inhibiting release of dopamine block amphetamine-induced stereotypy and enhance apomorphine-induced stereotypy, whilst compounds stimulating the release of dopamine potentiate amphetamine-induced stereotypy and inhibit apomorphine-elicited stereotyped behavior, it is likely that naloxone stimulates and morphine inhibits the release of DA following their acute administration.

Amphetamine↗
PubMed1983

Long-lasting effects of early barbiturates on central nervous system and behavior.

Forty years of prescribing barbiturates to pregnant women and infants, and thirty years of animal research have shown that barbiturates affect the developing central nervous system (CNS) and behavior. This paper compiles and reviews animal and selected human literature in this research area. Early barbiturate exposure in animals reduces brain weight with related changes in brain biochemistry and neuromorphology. Significant changes may be found in surviving adult offspring. Evidence of CNS and behavioral damage in human beings due to early barbiturate exposure is not clearcut, however, confounded by the conditions for which the drugs are prescribed. In animals, early drug exposure significantly reduces levels of hormones, vitamins, and other biologically active macromolecules via (long-lasting) induction of hepatic metabolizing enzymes. Whether or not in humans treated with barbiturates, hormone levels remain within the normal range (by-feed-back regulation) and, also, if vitamin deficiencies can be simply corrected by supplements is still being debated. Early barbiturates administered to animals is associated with long-lasting disturbances in activity, learning performance, sexual behavior, and reproductive function, but not in a simple dose-exposure related manner. Animal studies show that long-lasting functional tolerance to drugs develops following early barbiturate exposure. Although infants become "passively addicted" following in utero exposure, there is as yet no data on subsequent development of human adult tolerance. Drug related damage must, in any case, be weighed against therapeutic benefits of drug administration and the results of failure to treat.

Animals↗