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B Tabakoff

Publications and source records attributed to B Tabakoff.

At least 181 records · Page 10Linked to original sources
PubMed1981

Audiogenic seizures and neuronal deficits following early exposure to barbiturate.

Sabra mice (n = 232) received phenobarbital (PhB) during the period of their prenatal development (PB group), or during the period of their neonatal development (NB group). PB mice received the barbiturate transplacentally by feeding their mothers PhB in their diet (3 g/kg food) on gestation days 9-18. NB mice received daily injections of PhB on postnatal days 2-21. On postnatal days 28-31 subjects were tested for their susceptibility to audiogenic seizures. Only 10% of the PB mice seized, a rate similar to the 13% of controls. However, the seizure rate of NB mice was three times higher than controls (37%, p less than 0.001). Sample groups were kept until day 50 and their brains removed and saved for quantitative histological analysis of the hippocampal neurons. In PB mice, there was only a small deficit in the number of the hippocampal pyramidal neurons compared to controls (15%, p less than 0.01), and no deficit in the granule cells. On the other hand, NB mice sustained a 35% deficit in the number of the pyramidal cells (p less than 0.001) and a 21% deficit in the granule cells (p less than 0.01). The sensitive period for the neuronal damage corresponded with the sensitive period for changes in seizures. Although other parts of the brain are also involved in seizure, the correlationi of the seizure with the hippocampus is important because the hippocampus is one of the major structures determining seizure.

Acoustic Stimulation↗
PubMed1981

Centrally acting peptides and tolerance to ethanol.

Among the many factors that may influence the development or expression of functional tolerance to or physical dependence on ethanol is the neurohypophyseal hormone, arginine vasopressin (AVP). This peptide hormone, administered exogenously, maintains ethanol tolerance in animals once such tolerance has been established. An analog of the hormone has also been reported to facilitate the development of ethanol tolerance and to exacerbate ethanol withdrawal symptomatology. Neurohypophyseal hormones and structurally related peptides have previously been shown to influence learning or memory; however, structure-activity analyses reveal differences in the structural requirements for maintenance of ethanol tolerance as compared to facilitation of memory processes. Therefore, these phenomena may represent CNS adaptive processes which are subserved by different mechanisms, or are differentially sensitive to particular peptides. The initial sensitivity of an animal to ethanol can also be affected by peptides, notably thyrotropin releasing hormone (thyroliberin, TRH). TRH antagonizes many of the initial responses to ethanol, perhaps by non-specific means. AVP, however, appears to potentiate the sedative effect of an acute dose of ethanol. Neurohypophyseal peptides also modulate ethanol intake. Thus, these neuropeptides, which have been localized to many areas of brain, may serve as endogenous modulators of various parameters related to ethanol consumption.

Adrenocorticotropic Hormone↗
PubMed1981

Modification of environmentally cued tolerance to ethanol in mice.

Tolerance to the hypnotic and hypothermic effects of ethanol in mice develops with multiple injections. The tolerance to both of these effects of ethanol can be reduced by testing the animals in a novel environment, suggesting that the tolerance may be learned. Tolerance to the hypothermic effect of ethanol develops more rapidly than tolerance to the hypnotic effect. Disruption of the brain catecholamine systems, with either 6-hydroxydopamine or alpha-methyl-p-tyrosine slows the rate of development of tolerance to the hypnotic effect of ethanol. Intraventricular injection of the serotonergic neurotoxin 5,7-dihydroxytryptamine, increases initial sensitivity to ethanol-induced narcosis and facilitates the development of tolerance to the hypnotic effects of ethanol. Tolerance to the hypothermic effect of ethanol in a familiar environment is unaffected by either of the neurotoxins or by alpha-methyl-p-tyrosine. However, initial sensitivity to the temperature-lowering effect of ethanol is increased by 6-hydroxydopamine and decreased by alpha-methyl-p-tyrosine administration. Learning may be an important factor in development of tolerance to ethanol under some conditions and tolerance produced under these conditions can be modified by disruption of central catecholamine systems.

5,7-Dihydroxytryptamine↗
PubMed1980

Strain differences in the development of acute tolerance to ethanol.

C57B1/6 mouse brain serotonin levels were depleted by feeding animals a diet containing no tryptophan. When such mice were injected with ethanol, they were found to lose their righting reflex for significantly longer periods and to have a lower body temperature than control animals. Animals consuming the diet containing no tryptophan metabolized ethanol more slowly than controls. Although daily injections of kynurenine reinstated ethanol metabolism to normal, the duration of loss of righting reflex and the hypothermia induced by ethanol were unaffected by kynurenine pretreatment. Tryptophan (75 mg/kg) administered six hours prior to ethanol injection returned brain serotonin levels to normal in tryptophan-deprived mice. Mice injected with tryptophan were found to respond to ethanol as did the control animals. When brain ethanol levels were determined at the time the animals lost their righting reflex and when animals regained their righting reflex, tryptophan-deprived mice were found to regain the righting reflex at the same brain ethanol levels as those at which such animals lost their righting reflex. Tryptophan administration to tryptophan-deprived mice resulted in their regaining the righting reflex at higher ethanol levels than those at which they lost the reflex. Similar experiments were carried out on C3H/HeJ and DBA/J2 mice. The results indicate that C3H mice developed some acute tolerance while DBA mice failed to develop any acute tolerance. The possibility exists that the strain difference in the degree of sensitivity to ethanol observed in these mice may be due to differing abilities to develop acute tolerance.

Animals↗
PubMed1980

Modification of dopamine receptor-mediated processes after chronic ethanol intoxication: a possible mechanism.

Animals undergoing withdrawal from chronic ethanol treatment displayed significantly impaired function of dopaminergic systems in the CNS. Autonomic and behavioral response to dopaminergic agonists were reduced, as was the stimulation by dopamine of dopamine-sensitive adenylate cyclase from the striatal region of brain. In addition, the ability of neuroleptics to stimulate tryosine hydroxylase activity in the subcortex was diminished. These findings suggested a decreased sensitivity of dopaminergic receptors during ethanol withdrawal, and in time course of appearance and disappearance, the decreased sensitivity appeared to parallel ethanol withdrawal hyper-excitability. Moreover, the responsiveness of dopamine-sensitive adenylate cyclase could be restored by in vitro exposure to physiologically attainable concentrations of ethanol, suggesting that this system had become dependent on the presence of ethanol for normal function. The mechanism of the decreased sensitivity, in particular for the adenylate cyclase, but perhaps also for other dopamine receptor-mediated processesx, may be inefficient coupling between receptor and enzyme, as a result of changes in neuronal membrane structure produced by chronic exposure to ethanol and withdrawal.

Adenylyl Cyclases↗
PubMed1980

Receptor and membrane function in the alcohol tolerant/dependent animal.

Neurochemical changes which are associated with the development or expression of tolerance to or physical dependence on ethanol may be expected to display a time course of appearance and disappearance which correlates positively with the time course for tolerance or dependence. Previous studies of striatal dopaminergic receptor function indicated that ethanol-withdrawn mice displayed decreased physiological and biochemical responses to dopamine (DA) agonists, which could be best explained by postulating an inefficient coupling between DA receptors and various receptor-mediated processes, possibly as a result of ethanol-induced changes in neuronal membrane properties. The membrane-bound enzyme, (Na+-K+)ATPase, obtained from ethanol-withdrawn animals, displays an altered transition temperature and resistance to the effects of ethanol on enzyme activity. These changes also suggest compensatory alterations in neuronal membrane properties. All of these alterations show a time course of disappearance which corresponds to that for the disappearance of tolerance to the hypothermic and sedative effects of ethanol. Ethanol-withdrawn mice also display increased numbers of hippocampal muscarinic cholinergic receptors; however, the time course for the increase in receptor number appears to correlate with that of withdrawal symptomatology. Thus, compensatory changes in neuronal membrane properties in response to ethanol may be expressed via diverse functional changes.

Alcoholism↗
PubMed1980

Altered sensitivity to ethanol following prenatal exposure to barbiturate.

Female mice (genetically heterogeneous stock) were fed milled mouse food containing 3 g/kg phenobarbital (PhB) and water as their only nutritional source from gestation days 9-18. Control dams received milled food and water. Blood PhB levels of treated females and fetuses were 40-200 microgram/ml. At the age of 50 days, male offspring were injected with 3.5 g/kg ethanol. Sleep time was monitored and in randomly selected individuals, brain ethanol levels were determined upon awakening. To assess the rate of metabolism in the treated and control offspring, blood ethanol levels were determined in other randomly selected individuals at 60 and 120 min post-injection. Offspring who received PhB prenatally were resistant to the hypnotic effects of ethanol as evidenced by their 33% shorter sleep time compared to controls (P less than 0.001). The brain ethanol levels upon awakening were higher than control in the offspring born to the barbiturate-treated mothers (P less than 0.001), indicating that the resistance to ethanol was due to factors residing within the central nervous system.

Animals↗
PubMed1980

Neurohypophyseal peptide influences on ethanol tolerance and acute effects of ethanol.

The neurohypophyseal hormone, arginine vasopressin (AVP), was previously shown to prolong the duration of ethanol tolerance in mice. Since drug tolerance and certain memory-related processes are examples of CNS adaptation, these phenomena have been proposed to share underlying mechanisms. We investigated the effects on ethanol tolerance of two other neurohypophyseal peptides, both of which modulate memory consolidation or retrieval of information. (Des-9-glycinamide, 8-lysine) vasopressin (DGLVP), like AVP, maintained ethanol tolerance in C57Bl mice, while cyclo(Leu-Gly) (cLG), at an equimolar dose, was ineffective. Thus, various neurohypophyseal peptides may differentially influence CNS adaptive phenomena. Direct peptide effects on ethanol-induced hypothermia and "sleep time," the parameters used to evaluate ethanol tolerance, were also determined. AVP per se caused hypothermia in mice, but neither AVP nor cLG affected ethanol-induced hypothermia. Both peptides, however, increased "sleep time" after acute ethanol administration. Although these direct peptide-ethanol interactions do not account for the observed peptide effects on tolerance, the findings emphasize the importance of using several parameters to assess ethanol tolerance.

Animals↗
PubMed1980

Characterization of acute and chronic tolerance in mice selected for inherent differences in sensitivity to ethanol.

Long sleep (LS) and short sleep (SS) mice have been selectively bred for differences in response to hypnotic doses of ethanol. In these studies, SS mice were found to develop functional tolerance faster than LS mice during a regimen of multiple injections of ethanol. No evidence for the development of acute tolerance was evident in mice of either of the selected lines or the offspring of an LS by SS cross (F1), and no metabolic tolerance developed during the 5-day alcohol treatment period.

Animals↗
PubMed1980

Receptor-mediated dopaminergic function after ethanol withdrawal.

Striatal dopamine (DA) synthesis, measured in vivo as accumulation of DOPA after aromatic amino acid decarboxylase inhibition, is increased by neuroleptics and decreased by DA agonists as a result of their interactions with regulatory receptors. A sensitive high performance liquid chromatography (HPLC) technique has been developed, which allows the evaluation of both increases and decreases in DOPA levels in response to agonists and antagonists, and simultaneously permits measurement of DA levels as an indication of DA neuronal activity. C57BL mice, after chronic ethanol treatment and withdrawal, demonstrate significantly decreased responses, in terms of DOPA accumulation and DA release, to both haloperidol, a DA antagonist, and apomorphine, a DA agonist. These effects cannot be interpreted as resulting either from DA receptor subsensitivity or supersensitivity, but suggest instead that coupling between DA receptors and tyrosine hydroxylase is perturbed by ethanol treatment.

Alcoholism↗
PubMed1980

Alterations in neurotransmitter function during the development of ethanol tolerance and dependence.

Current studies demonstrate that alcohol tolerance and alcohol dependence are neurochemically dissociable processes. Development of tolerance seems to be accompanied by changes in neuronal membrane structure which, in turn, affects the function of membrane-bound dopaminergic receptors. On the other hand, changes in cholinergic receptor number in certain brain areas may be responsible for certain signs of physical dependence during ethanol withdrawal.

Alcoholism↗
PubMed1980

Sodium-potassium-activated adenosine triphosphatase activity as a measure of neuronal membrane characteristics in ethanol-tolerant mice.

(Na+-K+) activated adenosine triphosphatase of mouse synaptosomal membranes is inhibited by high concentrations of ethanol. When membranes were obtained from mice made tolerant to and physically dependent on ethanol by chronic exposure to an ethanol-containing liquid diet, the enzyme was resistant to the inhibitory effects of ethanol. Arrhenius plots of synaptosomal (Na+-K+) activated adenosine triphosphatase from control animals revealed that ethanol added in vitro lowered the transition temperature and altered the Arrhenius activation energies of this enzyme. Enzyme from ethanol-tolerant animals had a lower transition temperature than that from control animals, and ethanol added in vitro had no effect either on transition temperature or on activation energy of enzyme from ethanol-tolerant animals. The occurrence of lowered transition temperature and resistance to ethanol-induced alterations in transition temperature of the enzyme from ethanol-tolerant animals most likely reflects changes in membrane composition. Changes in Arrhenius plots correlated in time with resistance to the inhibitory effects of ethanol on (Na+-K+) activated adenosine triphosphatase activity and the time course of disappearance of these effects was similar to that of the disappearance of functional tolerance to ethanol. The resistance to the effects of ethanol on membrane function may be related to ethanol tolerance evidenced by behavioral and physiological measurements.

Alcoholism↗
PubMed1979

The effect of selective lesions of brain noradrenergic systems on the development of barbiturate tolerance in rats.

A method for chronic infusion of barbiturates into the central nervous system of rats was developed and used to study the importance of noradrenergic systems in the development of barbiturate tolerance. Destruction of noradrenergic neurons by intraventricular administration of 6-hydroxydopamine or by specific lesions of the dorsal or ventral noradrenergic bundles prevented the development of barbiturate tolerance without altering the animal's response to the acute administration of barbiturate.

Animals↗
PubMed1979

Cortexolone antagonizes development of alcohol tolerance in mice.

Mice treated with cortexolone during a period of chronic ethanol feeding displayed significantly less tolerance to a challenge dose of ethanol than mice fed ethanol but not given cortexolone. This glucocorticoid receptor blocker did not alter the hypnotic effects of ethanol in animals not previously given ethanol and no differences were found in ethanol consumption or blood ethanol levels between ethanol-fed mice receiving daily injections of cortexolone and the vehicle-injected controls. It was concluded that cortexolone interferes with the development of tolerance to ethanol.

17-Hydroxycorticosteroids↗
PubMed1979

Increased tolerance in mice following prenatal exposure to barbiturate.

HS/Ibg (heterogeneous stock) mice dams were fed milled mouse food containing 3 g/kg phenobarbital (PhB) in acid form and water as their only nutritional source from gestation days 9--19. Control females received milled food and water. Blood PhB levels of treated females and fetuses were 40--200 micrograms/ml blood. At the age of 50 days, male offspring were injected with C14 -sodium pentobarbital (PenB) (50 mg/kg). Sleep time and temperature loss were monitored and, in randomly selected individuals, brain PenB levels were determined upon awakening. The experiment was repeated on the same animals for 3 consecutive days. All offspring developed functional (central nervous system) tolerance during the 3 testing days as evidenced by the daily decrease in sleep time while brain levels of PenB upon awakening increased (P less than 0.001). Offspring who received PhB prenatally had generally shorter sleep times, less temperature loss, and higher brain PenB levels upon awakening than controls. The differences were most pronounced on the second day (sleep time reduced 27%, P less than 0.001; temperature loss 47%, P less than 0.001; brain PhB levels increased 23%, P less than 0.01).

Animals↗