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Biomedical subjects

B Tabakoff

Publications and source records attributed to B Tabakoff.

At least 145 records · Page 8Linked to original sources
PubMed1985

Ethanol increases plasma vasopressin shortly after intraperitoneal injection in rats.

In rats, ethanol has generally been thought to inhibit vasopressin (VP) release into the peripheral circulation; however, the primary evidence for this conclusion has been indirect. Radioimmunoassay was used to measure VP in the plasma of rats decapitated 5 or 60 min after intraperitoneal injection of ethanol (2.0 g/kg). Confirming the popular notion that ethanol inhibits VP release, VP levels were decreased 60 min after treatment. But radioimmunoassay techniques also revealed that VP release is markedly stimulated shortly after an injection of ethanol.

Animals↗
PubMed1985

Glial and neuronal glutamate transport following glutamine synthetase inhibition.

Glutamate transport into striatal tissue preparations was studied following inhibition of glutamine synthetase with methionine sulfoximine (MSO). Glutamate uptake in striatal tissue prisms was elevated for up to 7 days following an intraventricular (i.c.v.) injection of MSO. Kinetic analysis of glutamate uptake revealed that a high- and a low-affinity carrier system mediated the transport of glutamate into tissue slices. MSO altered the transport of glutamate via the high-affinity carrier without changing the characteristics of low-affinity glutamate transport. MSO increased the Km for glutamate and the Vmax at the high-affinity uptake site. The changes in the Km and the Vmax for glutamate uptake were maximal 24 hr after administration of MSO, but the transport system returned to normal by 14 days after injection. In addition, MSO increased high-affinity aspartate uptake into tissue slices, but it was without effect on leucine uptake. Glutamate uptake into striatal synaptosomes and bulk-isolated glial cells or neurons was, in all cases, mediated by a low- and high-affinity carrier. The Km and Vmax values for high-affinity glial-glutamate uptake were increased 24 hr after i.c.v. injection of MSO, while the low-affinity kinetic parameters for glial glutamate uptake were not altered by MSO. Neither high-affinity nor low-affinity glutamate uptake into bulk-isolated neurons or synaptosomes was altered by MSO 24 hr after injection. These results suggest that MSO induced alterations in glutamate transport within striatal slices may be due to changes in glial glutamate transport arising from the disruption of glutamate metabolism.

Animals↗
PubMed1985

Features of environment-dependent tolerance to ethanol.

Mice given multiple injections of ethanol in a standardized environment develop environment-dependent tolerance to the hypnotic and hypothermic effects of ethanol. These animals also demonstrate environment-dependent cross-tolerance to the hypnotic and hypothermic effects of pentobarbital. Examination of the levels of ethanol in the brain and blood at various times after injection of a test dose of ethanol, as well as the examination of the rate of disappearance of ethanol from the blood, indicated that environment-dependent tolerance could be explained by dispositional factors. On the other hand, mice rendered tolerant to ethanol by a liquid diet technique demonstrate tolerance that is not environment-dependent, and there is no alteration in ethanol levels in different environments for animals fed the liquid diet. When the animals in either paradigm are tested by injecting ethanol directly into the brain, tolerance is observed that is not dependent on the environment. Tolerance produced by these two different paradigms is apparently due to different adaptive strategies used by the animal. Environment-dependent tolerance is partially related to the ability of the animal to change the disposition of ethanol, while environment-independent tolerance may be entirely due to other factors, such as changes in neuronal sensitivity to ethanol.

Analysis of Variance↗
PubMed1985

Ethanol inhibits the activity of the B form of monoamine oxidase in human platelet and brain tissue.

Ethanol selectively inhibits the activity of the B-form of monoamine oxidase (MAO) in membranes obtained from human platelet and brain. When endogenous concentrations of phenylethylamine are used as substrate, significant inhibition is induced by concentrations of ethanol that are attainable after ethanol ingestion (50 mM). The mechanism of ethanol's inhibition of MAO activity appears to involve perturbation of membrane lipids surrounding the enzyme.

Aged↗
PubMed1985

Pentobarbital-induced drinking does not rely on a renal dipsogen.

Injections of pentobarbital have been shown to produce drinking in both deprived and nondeprived rats and a number of other studies have shown that pentobarbital is a potent renin releasor. Since renin has been shown to be involved in thirst regulatory mechanisms and since the dipsogenic actions of other renin-releasing agents have been blocked by nephrectomy, we sought to determine whether or not pentobarbital-induced drinking relies on a renal dipsogen. Rats were either "sham" operated or nephrectomized under ether anesthesia. Five to six hours later, animals in each group were injected with either 9.5 mg/kg pentobarbital sodium or vehicle, and intakes were measured 60 minutes later. Statistical analysis of water intakes indicated that pentobarbital produced significant drinking in both control operated and in nephrectomized rats, and that the intakes in these two groups did not differ. These results indicate that pentobarbital-induced drinking is not secondary to increased plasma renin activity and may suggest the involvement of central mechanisms in the drinking response.

Animals↗
PubMed1985

The development of type I and type II benzodiazepine receptors in the mouse cortex and cerebellum.

The postnatal development of benzodiazepine (BDZ) receptors was monitored in Heterogeneous Stock (HS) mice, and the BDZ receptors were characterized and categorized into Type I and Type II receptors. When the number of 3H-Flu binding sites (Bmax) was assessed at weekly intervals after the birth of the animal, the number of sites in both the cortex and cerebellum increased significantly if the data was expressed as fmol/mg tissue. On the other hand, no significant change in 3H-Flu binding sites was evidenced in the cortex, and the number of 3H-Flu binding sites in the cerebellum decreased during postnatal development if Bmax values were expressed as fmole/mg protein. When receptor binding data was analyzed for the presence of Type I and Type II BDZ receptors, the changes in KD values for 3H-Flu binding development could be accounted for by changes in relative proportions of Type I and Type II receptors present in the cortex and cerebellum during the maturation process. Type II receptors predominated in both cortex and cerebellum at birth, and Type I receptors proliferated primarily during the first two weeks of postnatal life. In the cortex of adult mice there were approximately equal numbers of Type I and Type II BDZ receptors. In the cerebellum of adult mice, computer assisted analysis of binding data could not distinguish the presence of two distinct BDZ binding sites. However, Hill coefficients and overall binding constants determined from data on CL-218,872 displacement of 3H-Flu binding to cerebellar membranes indicated that cerebellar tissue from adult mice did contain a heterogeneous array of BDZ receptors.

Aging↗
PubMed1985

Failure to establish a conditioned place preference with ethanol in rats.

Previous studies have demonstrated that many drugs of abuse are able to produce a conditioned place preference in rats. We sought to determine if ethanol, injected in a wide range of doses, could also produce a conditioned place preference. Statistical analysis of our results indicated that the IP administration of the drug (50, 100, 150, 300, 600, 800, or 1000 mg/kg) failed to produce either a conditioned place preference or aversion compared to vehicle injected control rats. Under similar testing conditions a conditioned place preference was obtained with amphetamine (2 mg/kg) and this preference was not secondary to conditioned hyperactivity. In another experiment, rats were injected with ethanol through indwelling jugular cannulae at doses similar to those reported [24,26] to support (1, 2 mg/kg) or not to support (8 mg/kg) self-administration by rats. We also failed to obtain a conditioned place preference using these doses. Blood and brain ethanol levels, determined 1, 2 or 5 minutes after the administration of 2 mg/kg (IV) indicated very low ethanol levels. These results may suggest that rats do not self-administer ethanol for its intoxicating properties, and that the affective state produced by ethanol administration per se is not readily conditionable to environmental cues.

Amphetamine↗
PubMed1985

Heterogeneity of brain benzodiazepine receptors: effects of physiological conditions.

A number of investigators have shown compelling evidence for multiplicity of benzodiazepine (BDZ) receptors. The present study addresses the query of BDZ receptor heterogeneity, in vitro, with respect to temperature. In competition studies involving rat cerebellar tissue, CL 218,872 produced Hill slopes near unity at both 0 degree C and 37 degrees C. In contrast, similar experiments utilizing cortical tissue from rats and mice produced Hill slopes of 0.69 and 0.66 at 0 degree C and 37 degrees C respectively. 3H-Flunitrazepam-photoaffinity labeling of cortical and cerebellar membranes was conducted at 0 degree C and 37 degrees C. SDS-PAGE fluorographic analyses of photolysed 3H-flunitrazepam (3H-Flu) revealed one intensely labeled 51K band in the cerebellum at both temperatures, which was specifically chased by diazepam. Similar experiments conducted in cortical tissue revealed photoaffinity labeling of at least three distinct macromolecules, one intense 51K and two less intense 55K and 59K bands. Labeling of each of these bands was chased specifically by diazepam. These data, taken together, indicate the existence of regional BDZ receptor heterogeneity under physiological conditions.

Animals↗
PubMed1985

Ethanol's effects on cortical adenylate cyclase activity.

The effects of ethanol on beta-adrenergic receptor-coupled adenylate cyclase (AC) of mouse cerebral cortex were examined. The addition of ethanol (20-500 mM) to incubation mixtures containing cortical membranes demonstrated that ethanol could increase AC activity and potentiate the stimulatory effects of guanylyl-imidodiphosphate [Gpp(NH)p] on AC activity. Ethanol increased the rate of activation of AC by guanine nucleotides and concomitantly decreased the EC50 for magnesium required to achieve maximal stimulation of cortical AC. The EC50 values for Gpp(NH)p and isoproterenol stimulation of AC activity were also altered by ethanol. Ethanol was capable of stimulating AC extracted by use of digitonin. The AC activity in the digitonin extract was no longer sensitive to the addition of Gpp(NH)p or NaF, but was still stimulated by ethanol. We propose multiple sites of action for ethanol in stimulating cortical AC activity. These sites include actions at the beta-adrenergic receptor, at the G/F coupling proteins, and at the catalytic unit of cortical AC. Comparison of ethanol's actions on cortical beta receptor coupled AC activity with prior reported actions of ethanol on striatal dopamine (DA)-sensitive AC indicated differential sensitivities of these two AC systems to ethanol. These differences may be determined by specific coupling characteristics of the striatal and cortical AC systems or by differences in the plasma membranes in which striatal and cortical AC systems are located.

Adenylyl Cyclases↗
PubMed1984

Intraventricular arginine vasopressin maintains ethanol tolerance.

Tolerance to the hypnotic effect of ethanol in mice is prolonged by once daily intraventricular injections of arginine vasopressin. This action is similar to that reported previously when vasopressin was administered subcutaneously. The results indicate that maintenance of ethanol tolerance by vasopressin is a centrally mediated action of the peptide, and is not due to possible aversive properties of peripherally administered vasopressin.

Analysis of Variance↗
PubMed1984

Specific effects of chronic phenobarbital administration on high- and low-affinity benzodiazepine receptors in mouse cerebellum and forebrain.

Characteristics of [3H]flunitrazepam ([3H]FLU) binding to cortical and cerebellar membrane receptors were examined following chronic (six days) administration of phenobarbital (PB) to C57B1 mice. Following PB treatment, the number of [3H]FLU binding sites (Bmax) was significantly reduced in both cerebral cortex and in cerebellum. No change in the affinity (KD) of these binding sites was observed. Using 3-methyl-6-[3-(trifluoromethyl)phenyl]-1,2,4-triazolo [4,3-beta]pyridazine (CL-218,872), further analysis revealed a significant decrease in the number of high-affinity CL-218,872 binding sites in cerebellar tissue. In the forebrain areas, however, a significant decrease in the number of low-affinity binding sites was found. Finally, the enhancement of [3H]FLU binding, produced by in vitro addition of pentobarbital, was significantly less pronounced in the cerebellum of PB-treated animals.

Animals↗
PubMed1984

A benzodiazepine antagonist action of CL 218,872.

The effect of the Type I benzodiazepine (BDZ) receptor agonist, CL 218,872, on convulsions generated by low doses of methyl beta-carboline-3-carboxylic acid ( MBCC ), bicuculline, picrotoxin and pentylenetetrazole (PTZ) in mice was examined. Low doses of CL 218,872 enhanced the convulsions produced by all agents except PTZ. An anticonvulsant action of CL 218,872 was observed at higher doses. Since CL 218,872 exhibits proconvulsive effects at low doses, and a proconvulsant action is a characteristic of compounds classified as BDZ antagonists, it appears that CL 218,872 has some antagonist action.

Animals↗
PubMed1984

A conditioning model of alcohol tolerance.

Tolerance to several effects of ethanol can be learned in a classical conditioning paradigm. In the conditioning model of tolerance, a response compensatory in nature to the effect of ethanol develops in association with the cues that signal the presence of ethanol. Tolerance produced by this procedure (environment-dependent tolerance) differs in several respects from tolerance produced in a paradigm in which learning would not be expected to play a significant role (environment-independent tolerance). Depletion of norepinephrine in the brain blocks the development of both types of tolerance, whereas depletion of serotonin enhances the rate of development of environment-dependent tolerance, but inhibits the development of environment-independent tolerance. Cued alterations in the volume of distribution for ethanol are an important factor in the tolerance displayed in the classical conditioning paradigm. It has been suggested that the conditioned compensatory response comprises the physiological response underlying "craving" for ethanol. This implies that an extinction procedure would be an effective treatment for the prevention of relapse.

Alcohol Drinking↗
PubMed1984

Alteration of striatal glutamate release after glutamine synthetase inhibition.

The effect of the glutamine synthetase (GS) inhibitor, methionine sulfoximine (MSO), on glutamate levels in, and glutamate release from, rat striatal tissue was examined. Tissue levels of glutamate were unchanged 24 h after an intraventricular injection of MSO, but tissue glutamine levels were decreased 50%. Calcium-dependent, potassium-stimulated glutamate release was diminished in tissue prisms from animals pretreated with MSO compared to controls. The decreased release of glutamate correlated over time with the inhibition of GS following an intraventricular injection of MSO. The maximum diminution of calcium-dependent, potassium-stimulated glutamate release (50%) and the maximum inhibition of GS activity (51%) were observed 24 h after MSO. The addition of 0.5 mM glutamine to the perfusion medium completely reversed the effects of MSO pretreatment on calcium-dependent, potassium-stimulated glutamate release. Since GS is localized in glial cells and the measured glutamate release is presumed to occur from neurons, the data support the contention that astroglial glutamine synthesis is an important contributor to normal neuronal neurotransmitter release.

Animals↗
PubMed1984

Effects of ethanol, temperature, and endogenous regulatory factors on the characteristics of striatal opiate receptors.

Ethanol can alter the affinity of mouse striatal opiate receptors for their ligands, and the present studies were aimed at determining the importance of the receptor microenvironment for this effect of ethanol. Changing the temperature of the binding assay, and thus altering the properties of neuronal membrane lipids, resulted in changes in the observed affinity of striatal binding sites for dihydromorphine (DHM), but not for D-Ala2, D-Leu5-enkephalin (ENK). The changes in temperature also differentially altered the response of the two binding sites to ethanol. Two other factors that regulate opiate receptor affinity, Na+ and GTP, also affected the response to ethanol. High concentrations of ethanol were more effective at decreasing receptor affinity for both DHM and ENK when the binding assays were performed in the presence of GTP or Na+. In addition, at 37 degrees C and in the presence of GTP or Na+, DHM binding, but not ENK binding, was significantly inhibited by a low, physiologically attainable concentration of ethanol. Our results suggest that the response of opiate receptors to ethanol is influenced by the microenvironment of the receptors, including the physical state of the membrane lipids and/or by the nature of the interactions of receptors with "coupling proteins" within the membrane. The differential responses of mu and delta receptors to temperature and to ethanol suggest that these receptors reside in specific membrane environments. Under physiological conditions, several different factors may contribute to a selective action of ethanol on particular subtypes of opiate receptors.

Animals↗
PubMed1984

Neurohypophyseal peptides maintain tolerance to the incoordinating effects of ethanol.

Arginine vasopressin (AVP), lysine vasopressin (LVP) and [des-9-glycinamide]LVP (DGLVP), administered systemically, delayed the disappearance of functional tolerance to the motor-incoordinating effect of ethanol in mice. This result is consistent with previous findings that AVP and related neuropeptides maintain tolerance to the sedative-hypnotic and hypothermic effects of ethanol, and suggests that the peptides modulate the rate of disappearance of tolerance per se, rather than simply influencing the tests used to evaluate tolerance. However, both the duration of tolerance to the incoordinating effect of ethanol, and the duration of peptide maintenance of this tolerance, were less than those observed for tolerance to the hypnotic and hypothermic effects of ethanol. Tolerance to various effects of ethanol clearly can develop and dissipate at different rates, and our results suggest that the characteristics of the maintenance of ethanol tolerance by neurohypophyseal peptides are influenced, to some extent, by the neural systems which mediate the expression of the functional tolerance which is being investigated.

Animals↗