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J J Feigenbaum

Publications and source records attributed to J J Feigenbaum.

At least 37 records · Page 2Linked to original sources
PubMed1987

Diethylstilbestrol counteracts barbiturate narcosis and hypothermia in male mice.

Treatment with DES one hour prior to pentobarbital injection resulted in diminution of the narcotic sleep and hypothermia usually found after pentobarbital (50 mg/kg 1) injection in male mice. The effect was biphasic: significantly countered relative to saline pretreated controls at low (.001-.10 mg/kg 1) and at high (10-50 mg/kg -1) DES doses only. Giving DES alone did not change core body temperature compared to saline injected controls, at either 25 degrees C or at 33 degrees C. At 33 degrees C, neither PeB narcosis nor body temperature loss was significantly inhibited by DES. Possible cytoplasmic, nonsex differentiated bases for these estrogen effects on barbiturate action in the brain is discussed.

Animals↗
PubMed1987

Stereochemical requirements for cannabimimetic activity.

The SAR of cannabimimetic activity in the cannabinoid series are reviewed with emphasis on the stereochemical requirements. Some new results are presented. The most important are that a, in humans, (-)-(1S)-delta-3-THC is much more active than (+)-(1R)-delta-3-THC; and b, with the 7-OH-delta-6-THC DMH enantiomers (32) and (33), the activity in several animal species resides completely in the (-)-(3R, 4R) enantiomer (32), the difference between the two enantiomers being up to several thousand times. The (3R,4R)-enantiomer (32) is much more active than delta-1- or delta-6-THC in animal tests, the exact level of activity depending on the test employed. The cannabimimetically inactive (+)-(3S,4S) enantiomer (33) was shown to be a potent analgetic in several animal tests. Thus, a complete dissociation between the cannabimimetic and the analgetic effects in a cannabinoid has been achieved, apparently for the first time.

Analgesics↗
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↗
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↗
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

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

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↗
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

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↗