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R E Hruska

Publications and source records attributed to R E Hruska.

At least 19 recordsLinked to original sources
PubMed1989

Species differences in estrogen receptors and in the response to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure.

The acute toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exhibits marked interspecies variability, with the guinea-pig, rat and hamster representing the species most sensitive, intermediate and most resistant to acute toxicity. Prepubertal guinea-pigs, rats and hamsters were treated with a single intraperitoneal injection of TCDD in olive oil at doses of 4, 50 and 1500 micrograms/kg, respectively. These exposures were chosen to produce acute toxicity and all 3 species exhibited a decrease in the rate of body weight gain during the 7 days following TCDD exposure when compared with control (olive oil-treated) animals. On the 7th day after exposure, the density and affinity of 17 beta-estradiol receptors were determined in the uterus and liver of TCDD-treated and control animals. The treatment with TCDD did not alter the affinity of the receptors in these 3 species. The density of hepatic 17 beta-estradiol receptors was decreased 65% in the guinea pig and 92% in the rat following exposure to TCDD. In contrast, TCDD-treated hamsters exhibited no change in the density of hepatic 17 beta-estradiol receptors. The uterine 17 beta-estradiol receptors were increased in density by TCDD treatment in the hamster and in the rat when expressed per mg protein. Uterine wet weights in the guinea-pig and rat were also significantly decreased by TCDD treatment but were not changed in the hamster. When the Bmax for uterine 17 beta-estradiol receptors was expressed as pmol/g tissue wet weight. TCDD exposure was found to produce an 11% decrease in density in the rat, while producing a 44% increase in the hamster. In control animals, the density of uterine 17 beta-estradiol receptors correlated inversely with the lethal dose of TCDD in these 3 species (i.e., the guinea-pig has the lowest LD50 and highest density of uterine 17 beta-estradiol receptors). The different responses to TCDD in the 3 species suggest that the changes in 17 beta-estradiol receptors may be related to species-specific toxic responses associated with TCDD exposure.

Animals↗
PubMed1988

Kainic acid lesions decrease striatal dopamine receptors and 1,4-dihydropyridine sites.

The effects of intrastriatal injection of kainic acid (2 microliters, 1 mg/ml) in the rat were determined. Four weeks after the lesioning, striatal dopamine receptors and 1,4-dihydropyridine sites were measured by radioligand binding with [3H]spiperone and [3H]nimodipine, respectively. Dopamine receptor and 1,4-dihydropyridine binding densities were decreased by 58% and 43% respectively, with no change in binding affinity for either ligand. 1,4-Dihydropyridine-sensitive Ca2+ channels may be located primarily on postsynaptic elements.

Animals↗
PubMed1988

Estrogen treatment increases the density of D1 dopamine receptors in the rat striatum.

Adult, male rats were treated with 17 beta-estradiol valerate by s.c. injection of 125 micrograms/rat. Six days later the density and affinity of striatal D1 dopamine (DA) receptors were determined. Estrogen treatment significantly increased the density of D1 DA receptors without altering their affinity. In vitro co-incubation with 17 beta-estradiol 17 beta-estradiol valerate at concentrations up to 1.0 microM did not alter binding to D1 DA receptors.

Animals↗
PubMed1988

Effect of ethanol administration of striatal D1 and D2 dopamine receptors.

Chronic in vivo exposure of rats to ethanol in a complete liquid diet for 14 or 21 days produced a behavioral tolerance to the acute injection of ethanol. After 21 days, but not 14 days, of chronic exposure, there was a significant increase in the maximum density of striatal D1 and D2 dopamine receptors without a change in these receptors' affinities. A 24-h withdrawal from the 21-day exposure did not alter the observed increase in density. Both the level and duration of ethanol exposure appear to be important variables for demonstration of an increase in striatal D1 and D2 dopamine receptors.

Animals↗
PubMed1987

Influence of hypophysectomy on dopamine receptors and dopaminergic behaviors.

Hypophysectomy (Hypox) has been proposed to alter the behavioral and biochemical indices of striatal dopamine (DA) function. Since the regulation of striatal DA receptors by hormones may involve the pituitary, it was relevant to reevaluate the effects of Hypox in male and female rats. Behaviorally, dopaminergic agonists exerted enhanced activity in Hypox male and female rats. It has been suggested that these changes are due to altered metabolism since no increase in the DA receptor populations was observed. Dopaminergic antagonists showed equivalent behavioral actions in male and female rats, whether intact or Hypox. Biochemically, neither the density nor the affinity of the striatal DA receptors is altered by Hypox in female rats for 1-2 weeks or male rats for 5-6 weeks. However, in female rats at 5-6 weeks after Hypox there is a significant decrease in receptor number. This decrease in density is not reflected in behavioral changes to either DA receptor agonists or antagonists. Therefore, all dopaminergic behavioral changes do not result from alterations in DA receptors and changes in DA receptors do not necessarily dictate altered behavioral responses to dopaminergic agents.

Animals↗
PubMed1986

Hypophysectomy does not alter the increase in striatal dopamine receptor density produced by 6-hydroxydopamine lesions in male rats.

While hypophysectomy can alter the increase in striatal dopamine (DA) receptor density observed after estrogen, haloperidol or prolactin treatments, it does not alter the increase in density found after 6-hydroxydopamine lesions of the DA neurons in male rats. This observation suggests that striatal DA receptors can be regulated by at least two distinct mechanisms, only one of which requires the availability of pituitary hormones.

Animals↗
PubMed1986

Modulatory role for prolactin in the elevation of striatal dopamine receptor density induced by chronic treatment with dopamine receptor antagonists.

The chronic administration of haloperidol (HAL), domperidone (DOM), or sulpiride (SUL) increased the density of striatal dopamine (DA) receptors in intact but not in hypophysectomized (Hypox) male rats. This effect was independent of changes in body weight of the rats and of the drugs' abilities to produce cataleptic behavior. All treatments of intact rats increased serum rat prolactin (rPRL) concentrations, while Hypox rats had rPRL levels equivalent to zero. At the doses used in these studies, the striatal DA receptor densities were increased only if the rPRL levels were also increased. Chronic cysteamine (CYS) treatment decreased body weight gain, acutely decreased cataleptic behavior to HAL, decreased serum rPRL levels, and prevented the increase in serum rPRL levels due to HAL administration. While CYS itself did not alter striatal DA receptor density, it prevented the increase in density associated with the chronic administration of HAL (1 mg/kg). Since CYS decreased rPRL levels, these results lend further support to the hypothesis that rPRL (and prolactin in general) is a pituitary hormone with modulatory action on the increase in striatal DA receptor density.

Animals↗
PubMed1986

Elevation of striatal dopamine receptors by estrogen: dose and time studies.

Administration to male rats of a single dose of 17 beta-estradiol valerate (8-500 micrograms/rat) or implantation of a pellet containing 17 beta-estradiol (0.5-50 mg/rat) increased serum 17 beta-estradiol levels in a dose-dependent relationship when measured on the sixth day after administration. At the same time, after these doses, the serum rat prolactin (rPRL) levels were doubled and the striatal 3,4-dihydroxyphenylethylamine (DA, dopamine) receptor densities were increased 20%. A single dose of 17 beta-estradiol valerate of 4 micrograms/rat or less did not alter serum 17 beta-estradiol or rPRL levels or the striatal DA receptor density. After the single injection of 17 beta-estradiol valerate (125 micrograms/rat) the serum 17 beta-estradiol levels peaked at 1 day, the serum rPRL levels peaked at 2 days, and the striatal DA receptor density elevation peaked from 4 to 8 days. Implantation of a pellet containing 17 beta-estradiol (25 mg/rat) produced a constant elevation of serum 17 beta-estradiol levels from 1 to 10 days. Whereas the serum rPRL levels were continuously elevated about two-fold, the densities of the striatal DA receptors were increased significantly by 20-25% only from 4 to 8 days after pellet implantation. These results indicate that striatal DA receptor density rises and returns to control levels during the constant elevation of serum 17 beta-estradiol and rPRL levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

[3H]Spiperone binding in the rat striatum during the development of physical dependence on phencyclidine and after withdrawal.

Binding of [3H]spiperone to dopamine D2 receptors was measured in the striatum of male rats that were infused with phencyclidine (PCP, 45 mg/kg per day) or vehicle (saline) via an intrajugular cannula for 1, 3.5, or 7 days. The 7-day PCP infusion, which was shown previously to induce physical dependence, produced a significant 30% decrease in receptor density (Bmax). Two days after termination of the 7-day PCP infusion, Bmax values were no longer significantly lower than those of saline-infused controls. The acute administration of PCP (20 mg/kg, i.p.) did not alter receptor density 45 min later.

Animals↗
PubMed1985

Possible dissociation of central dopamine receptor antagonism and cataleptic behavior.

A new chemical, 2-[4-[4-(7,9-dioxo-6-thia-8-azaspiro[4,4] nonan-8-yl)-butyl]-1-piperazinyl]pyridine-3-carbonitrile hydrochloride (MJ-13980-1), referred to in this report as MJ-13980, displaced in vitro [3H]spiperone binding, elevated serum prolactin concentrations, and decreased apomorphine-induced stereotyped behavior in male rats. These indicated that MJ-13980 acts as a dopamine (DA) receptor antagonist. However, MJ-13980 (10 mg/kg) elicited only a very small amount of cataleptic behavior and antagonized that produced by haloperidol (HAL), a classical DA receptor blocker and potent inducer of cataleptic behavior. At a lower dose, MJ-13980 (1.0 mg/kg) produced no cataleptic behavior but against decreased that produced by HAL. These results suggest that the antagonistic interaction of MJ-13980 at central DA receptors is not associated with the production of cataleptic behavior.

Animals↗
PubMed1981

Inhibition of neurotransmitter receptor binding by ergot derivatives.

Bromocriptine, lergotrile, lisuride, metergoline, and the Sandoz ergot derivatives 25-397, 29-712, and 29-717 have been tested for their ability to inhibit the synaptic receptor binding of spiroperidol, 5-hydroxytryptamine (5-HT), d-lysergic acid diethylamide (LSD), quinuclidinyl benzilate (QNB), WB.4101, and gamma-aminobutyric acid (GABA). Only GABA binding was not affected, and QNB binding was decreased only by lergotrile and metergoline at high concentrations. The most potent inhibitors of the other ligands were bromocriptine and lisuride for spiroperidol (1-2 nMM), metergoline for 5-HT (29 nM), lisuride for LSD (15 nM), and lergotrile for WB.4101 (17 nM). The direct receptor effects of the ergot derivatives in vitro may contribute to understanding their in vivo effects on behavior and in predicting their therapeutic potential in neurological and neuroendocrine disorders.

Adrenergic alpha-Antagonists↗
PubMed1979

Effects of ergot drugs on serotonergic function: behavior and neurochemistry.

Several new ergot drugs were tested for behavioral and neurochemical effects related to serotonergic function. Lergotrile and bromocriptine potentiated the so-called "5-HT syndrome", a set of behaviours associated with increased serotonergic neurotransmission consequent to monoamine oxidase inhibition and tryptophan loading. Metergoline antagonized this behavior. In studies of receptor binding using 3H-5-HT or 3H-LSD, metergoline was the most potent at displacing specific ligand binding. Since the ergots also affect dopaminergic function, these results are discussed for their information on both dopaminergic and serotonergic actions of these drugs and their implications for clinical use of ergots.

5-Hydroxytryptophan↗
PubMed1979

Tremor: role of striatal cholinergic neurons and the effect of intrastriatal kainic acid.

Rats injected intrastriatally with kainic acid (KA) showed increased tremor responses to arecoline and tremorine, but not to harmaline. Since KA significantly reduced both pre- and postsynaptic measurements of cholinergic function in the striatum, the results indicate that integrity of the striatal cholinergic system is not essential to tremor response. Further investigations of cholinergic function in the brains of rats injected with KA did not reveal evidence of cholinergic supersensitivity; thus, the altered responses to cholinergic agents may reflect KA-associated destruction of some pathway normally opposing the behavioral output of cholinergic stimulation. If, as recently proposed, intrastriatal injection of KA produces an animal model of Huntington's disease (HD), then these results may also be relevant to experimental therapeutics of this disorder.

Animals↗