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J Yanai

Publications and source records attributed to J Yanai.

At least 91 records · Page 5Linked to original sources
PubMed1983

Evidence for the involvement of central dopaminergic receptors in the acute and chronic effects induced by barbiturates.

There is close agreement in the literature concerning the effect of specific and directly acting dopaminergic (DA) agonists and antagonists on acute barbiturate-induced responses; with DA agonists inhibiting and DA agonists potentiating these responses. On the other hand, there are presently no studies (and hence no evidence) regarding the effects of direct and specific alterations of DA receptor arousal on chronic barbiturate-induced tolerance or withdrawal. Concerning the effect of acute barbiturate administration on central dopaminergic responses; while some studies report no effect, there is some evidence that barbiturates block DA reuptake after their acute administration. This is consistent with and may explain findings that these drugs also decrease striatal DA turnover acutely, decrease DA concentration in synaptosomes, and decrease postsynaptic DA receptor arousal. In noting the potentiation of acute barbiturate-induced responses elicited by DA antagonists, it is interesting to observe that barbiturates and DA antagonists both apparently decrease receptor sensitivity and inhibit DA reuptake presynaptically. Moreover, the supersensitivity to DA agonists induced by chronic DA antagonist administration can be potentiated by barbiturates. Thus, barbiturates appear to block the arousal of postsynaptic DA receptors, though probably not those coupled to adenylate cyclase and, unlike neuroleptics, indirectly. It is likely that the inhibitory effect on DA receptor arousal exerted by barbiturates accounts for at least some of the central effects produced by these drugs.

Adenylyl Cyclases↗
PubMed1983

Adrenal glucocorticoids as a required factor in the development of ethanol tolerance in mice.

Male C57BL/6J mice were given chronic ethanol treatment by two procedures. One was by a liquid diet containing 6.4% (v/v) ethanol; the other was by repeated injections of ethanol (3.5 g/kg, i.p. twice daily). After 5 days of the liquid diet treatment, sleep time following a challenge dose of ethanol (3.0 g/kg i.p.) was reduced to 10 min as compared with 30 min in the controls not previously exposed to ethanol. After 10 days, none of the ethanol-treated animals slept. Bilateral adrenalectomy (Adx) had no effect on sleep time (34 min). However, the reduction of sleep time in ethanol-treated Adx animals was much less: 19 min after 5 days, and 20 min after 10 days. Replacement with corticosterone in Adx animals restored the reduction of sleep time to the same levels as intact animals, indicating that glucocorticoids are the hormonal factor involved in the Adx effect. By the injection procedure for short-term administration of moderate doses of ethanol, sleep time following the injection of 3.5 g/kg ethanol was reduced from 95 min on day 1 to 57 min on day 3. There was no difference between intact and Adx animals. The results from both treatment procedures suggest that Adx abolished the later, severe stage of tolerance development but not the initial stage. Functional tolerance to ethanol occurring in this advanced stage may be a glucocorticoid-dependent process.

Adrenalectomy↗
PubMed1983

Genetic factors influencing neurosensitivity to early phenobarbital administration in mice.

This study was designed to assess the possible genetic determinants of neurosensitivity to early (neonatal) phenobarbital (PhB) administration and to conduct a strain comparison for the cerebellar histology of both inbred and outbred mice. HS/Ibg, C57BL/10 and DBA/1 pups were injected with 50 mg PhB/kg daily on neonatal days 2-21. On day 50, treated animals (B) of all strains had smaller brains than controls (C). Moreover, the cerebellar area was decreased in HS and C57 B mice but not in DBA mice, suggesting genotype-environment interaction. B mice from all strains had similar Purkinje cell losses. Strain comparison showed that control C57 mice had smaller brains than control HS, and DBA had smaller brains than both HS and C57. Similarly, C57 had smaller cerebellar layers than HS and DBA had smaller cerebellar layers than both HS and C57. DBA and C57 mice had fewer Purkinje cells than HS but did not differ from each other.

Animals↗
PubMed1983

The combined effect of quipazine and haloperidol on plasma prolactin release.

The possible dopaminergic properties of the central serotonergic agonist quipazine was examined using plasma prolactin release as a model to determine whether quipazine exerts an agonist effect on only serotonin receptors or on dopamine receptors as well. Drugs acting on two different receptors have only an additive effect on the same parameter while different drugs acting on the same receptor exert a synergistic effect. Therefore we determined whether combining quipazine with haloperidol, which has no effect on serotonin receptors, would produce a synergistic or only an additive effect on prolactin release, relative to the release induced by quipazine alone. A distinct synergism was produced, suggesting that quipazine acts on both DA and 5-HT receptors. Moreover, the model used may be useful for distinguishing whether a given drug acts on one or two receptors concurrently.

Analysis of Variance↗
PubMed1983

Eight arm maze for mice.

Certain behaviors have been found to be mediated by the brain. Eight-arm maze behavior is a measure of spatial-memory, and the integrity of this has been connected with the integrity of the hippocampus in rats (Olton & Samuelson, 1976). Mice are useful animals in neuropharmacological research, but an apparatus for mice has not yet been developed, perhaps because mice were thought incapable of executing intricate tasks as compared with rats. We developed an eight-arm-maze adapted for mice to be used for such an experiment and also developed a procedure that was found to be highly useful and easy for mice to carry out, in order to increase their motivation to work in the apparatus. In our early studies we had shown that neonatal exposure to phenobarbital destroyed hippocampal neurons (Yanai & Bergman, 1981). Consequently, we used a sensitive eight-arm-maze to show that even small differences in performance can be clearly shown in this maze.

Animals↗
PubMed1983

Morphine may not produce true catalepsy.

Though catalepsy is one of the primary features classically associated with morphine injections in animals, several investigators have suggested that morphine may not produce true catalepsy. A study was therefore undertaken using the most widely accepted tests of catalepsy to determine whether a dose related catalepsy could be obtained in rats. The effect produced by morphine was then compared with the catalepsy elicited by subthreshold to suprathreshold doses of haloperidol. In the course of catalepsy assessment, it was found that half the tests employed could not distinguish between the several doses of morphine that were administered. Moreover, the cataleptoid behavior induced by morphine failed to satisfy nearly all of the criteria most widely used for catalepsy. This is in marked contrast to the results obtained with varying doses of haloperidol. These results are compatible with the suggestion that morphine may not be a true cataleptigenic agent.

Animals↗
PubMed1983

Possible dopamine agonist properties of quipazine maleate.

Though quipazine is widely regarded as a relatively pure serotonergic (5-HT) agonist and has been reported to have no dopamine (DA) agonist properties, it has produced stereotyped behavior (SB) associated with DA agonist arousal of striatal DA mechanisms. Since we observed a dose-related inhibition of quipazine induced stereotypy (QISB) by a centrally acting DA antagonist (haloperidol) that could not be mimicked by a central 5-HT receptor blocking agent (methysergide), it appeared likely that QISB is mediated by striatal DA mechanisms. This was further supported by our observing that QISB could be potentiated by a subthreshold dose of the central DA agonist apomorphine. In light of this, and the presence of abnormal movements seen concomitantly with QISB that are typically produced by intrastriatal injections of 5-HT agonists, it appears that QISB is a complex phenomenon. While QISB seems to be primarily due to the stimulation of DA mechanisms, the effect of quipazine on behavior appears to be a combined result of its effects on both DA and 5-HT mechanisms. Specifically, central striatal DA receptors appear to mediate QISB per se, while serotonergic mechanisms stimulated by quipazine inhibit its further development and produce extrapyramidal-like abnormal movements.

Animals↗
PubMed1983

Genetic factors in drug neuroteratogenicity.

The exposure in humans to ethanol or barbiturates during prenatal or neonatal development is common. There are indications that the magnitude of the resulting symptoms may be genetically determined. In the present article, an animal model was established for the study of the genetic determination of the neurosensitivity to ethanol and barbiturates administered during prenatal and/or neonatal development. Inbred C57BL/10 (C57) and DBA/1 (DBA) mice were employed in the ethanol studies and these strains and the outbred HS/Ibg (HS) were used in the barbiturate studies. Early ethanol administration induced a long lasting increase in the susceptibility to audiogenic seizures in both strains but to a greater degree in C57. Neuropharmacological studies implicated the serotonergic but not the noradrenergic system as mediating the early ethanol induced changes in audiogenic seizures. Open field activity was decreased but only in C57. Male agonistic behavior and predatory behavior were greatly reduced by early ethanol administration but mainly in DBA. Long term induction of the activity of the hepatic enzymes, alcohol dehydrogenase and microsomal ethanol oxidizing system, occurred in both strains after early exposure to ethanol. After early exposure to phenobarbital HS mice had long lasting increases in the susceptibility to audiogenic seizures and in the hippocampus related behaviors, spontaneous alternations and eight arm maze performance. The hepatic microsomal drug oxidizing system was induced in adult HS mice with early phenobarbital (PhB) exposure. Early PhB exposure also caused long term decreased sensitivity to ethanol narcosis and an accelerated acquisition to barbiturate tolerance, possibly mediated via a change in the sensitivity of the post synaptic dopamine receptors. Changes in the PhB treated offspring also included a reduction in the levels thyroid hormone. Early exposure to PhB resulted in a long term deficit in the area of brain layers, number of neurons, dendritic spines and the ultrastructure. Strain comparison suggested that DBA was less neurosensitive to early PhB administration than both HS and C57. It was concluded that genotype-environment interaction exists in the effect of drugs on the developing CNS.

Acoustic Stimulation↗
PubMed1983

Differential catecholamine uptake inhibition as a possible mode of action of D-amphetamine induced locomotor activity.

A determination was made of the roles played by the selective uptake inhibition versus release of dopamine (DA) or norepinephrine (NE) ex vivo in either the striatum or cerebral cortex in mediating d-amphetamine induced locomotor activity (AILA). Desmethylimipramine (DMI) and/or d-amphetamine variously effected the uptake of DA and NE in both regions in terms of the absolute amount of uptake inhibition elicited by each drug separately or by the two drugs administered concomitantly. However, none of the drug treatments produced a selective inhibition of DA or NE uptake in either the striatum or cerebral cortex. On the other hand, a selective inhibition of central DA release by gamma-hydroxybutyrate markedly inhibited AILA. These results suggest that amphetamine induced locomotor activity is not likely mediated by a preferential effect on DA or NE uptake. It is far more probable that AILA is induced by a stimulation of central DA release.

Animals↗
PubMed1982

The effect of drugs altering striatal dopamine levels on apomorphine induced stereotypy.

Drugs that increase or decrease striatal dopamine levels appear to affect apomorphine induced stereotypy. This finding was unexpected, as it has previously been maintained that drugs which exert any action on striatal DA terminals exclusively would affect only indirect dopaminergic agonists, as opposed to apomorphine which induces stereotypy by acting directly on postsynaptic dopamine receptors. Specifically, inhibiting intrastriatal dopamine levels inhibits this behavior. This effect is explained in terms of apomorphine having a greater intrinsic activity and agonist affinity for striatal dopamine receptors than dopamine itself. Thus, dopamine and drugs which promote its release, may diminish the central behavioral effects induced by apomorphine relative to drugs which inhibit dopamine release centrally.

Animals↗
PubMed1982

Early barbiturate treatment eliminates peak serum thyroxine levels in neonatal mice and produces ultrastructural damage in the brains of adults.

Serum thyroxine levels peak sharply at the end of the second postnatal week in mice. Treating neonatal mice with barbiturates (PhB) completely eliminates this marked thyroxine (T4) peak without significantly affecting nonpeak levels at other ages. PhB treatment at this same time also establishes or induces long-lasting degenerative processes that continue to result in ultrastructural neural deficits in adults, long after treatment has been discontinued. Similar neural deficits have been observed in animals which were deficient in T4 during this same period of development.

Aging↗
PubMed1982

Accelerated acquisition of ethanol tolerance in isolated mice.

Male mice were kept in isolation (isolated mice) or in groups of 8 mice per cage (grouped mice). After 6 weeks all mice received two daily intraperitoneal injections of 3.5 g/kg ethanol at 8 a.m. and 5 p.m., and sleep time was monitored after the a.m. injection. Brain ethanol levels upon awakening were assayed in sample groups. This procedure was repeated for 3 consecutive days. Isolated mice had a shorter sleep time than grouped mice (p less than 0.001) and they woke up with higher brain ethanol levels (p less than 0.01). Both groups had a progressive decline in sleep time during repeated ethanol exposure (p less than 0.001). However, isolated mice achieved the reduction in half the time it took grouped mice (p less than 0.001). The sleep time significantly correlated with brain ethanol levels upon awakening (r = -0.4967, p less than 0.001). It is suggested, therefore, that isolation in mice reduces brain sensitivity to ethanol and accelerates the rate of acquisition of functional tolerance to ethanol.

Animals↗
PubMed1982

Neuronal losses in mice following both prenatal and neonatal exposure to phenobarbital.

Mice were given phenobarbital (PhB) during neonatal development (NeoB group) and during pre- and neonatal development (Pre- and NeoB group). Prenatal exposure was accomplished transplacentally by feeding the pregnant mothers 3 g PhB/kg milled food on gestation days 9-18. Neonatal exposure was conducted directly by injecting the neonates daily with 50 mg PhB/kg on postnatal days 2-21. The brains of these animals were studied at age 50 days using H & E staining. Consistent with previous studies, NeoB animals had a 14-20% smaller cerebellar layer area than controls, 32% fewer cerebellar Purkinje cells and 34% fewer granule cells than controls. NeoB mice had a 14-18% smaller hippocampal layer and 17% fewer hippocampal pyramidal cells than controls. The number of the hippocampal granule cells was not reduced by early PhB administration. NeoB mice had an 18% smaller cerebral cortex area and 22% fewer cortical cells than controls. The pre- and NeoB animals did not differ from controls in the area of their cerebellar layers, but they did have fewer cerebellar Purkinje and granule cells. Similarly, the Pre- and NeoB animals did not differ from controls in the area of their hippocampal layers, but they had fewer pyramidal cells. The Pre- and NeoB animals had a smaller cerebral layer area than controls but did not differ significantly from controls in the number of cortical neurons. It was suggested that exposure to PhB during prenatal and neonatal periods is not additive. On the contrary, tolerance or compensatory mechanisms may develop after prenatal exposure and lessened the effect of subsequent neonatal PhB exposure.

Animals↗
PubMed1982

Morphological alterations in the medial preoptic area after prenatal administration of phenobarbital.

Pregnant Sabra mice received 3 g phenobarbital per kilogram milled food from gestational days (GD) 9 to 18 as their only food source; control females received milled food. All the females were divided into three groups and injected intraperitoneally with a single dose of 3H-thymidine on GD 13, 15 or 17. At 50 days of age of the offspring were perfused with 10% neutral formalin and their brains removed and prepared for autoradiography. Matching sagittal sections of the offspring were selected for the study of the medial preoptic area (MPOA) of the hypothalamus. The total number of cells per section was not significantly different between males and females, however, there was a greater cellular packing density (cell/mm2) in females (p less than 0.05). This sex difference disappeared in treated offspring, possibly due to a 76% decrease on GD 13 in the rate of cell proliferation in females (number of labeled cells but not in males (p less than 0.001); the greatest decrease in the number of labeled cells occurred in the sexually dimorphic areas of the MPOA (p less than 0.001). The area of the sagittal section of the MPOA did not differ significantly between sexes or treatments.

Animals↗
PubMed1982

Possible DA agonist properties of naloxone.

Naloxone is widely if not universally considered to be a pharmacologically 'pure' opiate (mu) receptor antagonist virtually devoid of agonist action when administered in moderate dosages. However, naloxone (NX) appears to possess a striking number of DA agonist properties. Thus, some investigators have found NX capable of inducing stereotyped rearing and locomotor activity in habituated rats (a controversial finding), and decrease serum prolactin levels, improve Parkinsonism, enhance copulatory performance in sexually sluggish animals, and increase striatal HVA levels, in mimicry of centrally acting DA agonists. NX can also significantly potentiate the central effects induced by DA agonists including DA agonist (d-amphetamine) induced 3H-dopamine release, and antagonize a number of the central effects elicited by DA release inhibiting agents. Finally, virtually all of the central effects of morphine reversible by NX have also been found to be antagonized by a variety of dopamine agonists; while DA release inhibiting agents can abolish the ability of NX to antagonize morphine induced effects. Thus, NX may be exerting its central effects through a dopaminergic mechanism. Since NX does not bind DA receptors, it is quite likely that NX may ultimately antagonize the central effects of morphine by enhancing DA release from DA terminals upon which opiate receptors are localized. The same opiate receptors, shown to be localized on DA nerve terminals, have already been implicated in opiate mediated modulation of DA release.

Animals↗