Biomedical subjects

W A Hunt

Publications and source records attributed to W A Hunt.

At least 55 records · Page 3Linked to original sources

PubMed1986

Angiotensin II-induced taste aversion learning in cats and rats and the role of the area postrema.

The capacity of angiotensin II (AII, 1 mg/kg, IP) to produce a taste aversion was studied in cats and rats with and without lesions of the area postrema. Using a one-bottle test, injection of AII produced an aversion in cats but not in rats. Using a two-bottle test, injection of AII produced a slight, but significant, decrease in sucrose preference in intact rats, but had no effect on rats with area postrema lesions. Lesions of the area postrema prevented the acquisition of a taste aversion in cats. These results, which show a clear species difference in the capacity of AII to produce a taste aversion, are discussed as supporting the hypotheses that there is a relationship between the sensitivity of the area postrema to a compound and the capacity of that compound to produce a taste aversion; and that excitation of the area postrema constitutes a sufficient condition for taste aversion learning to occur.

Angiotensin II↗

PubMed1986

Mechanisms of radiation-induced conditioned taste aversion learning.

The literature on taste aversion learning is reviewed and discussed, with particular emphasis on those studies that have used exposure to ionizing radiation as an unconditioned stimulus to produce a conditioned taste aversion. The primary aim of the review is to attempt to define the mechanisms that lead to the initiation of the taste aversion response following exposure to ionizing radiation. Studies using drug treatments to produce a taste aversion have been included to the extent that they are relevant to understanding the mechanisms by which exposure to ionizing radiation can affect the behavior of the organism.

Amphetamine↗

PubMed1986

Ionizing radiation alters the properties of sodium channels in rat brain synaptosomes.

The effect of ionizing radiation on neuronal membrane function was assessed by measurement of neurotoxin-stimulated 22Na+ uptake by rat brain synaptosomes. High-energy electrons and gamma photons were equally effective in reducing the maximal uptake of 22Na+ with no significant change in the affinity of veratridine for its binding site in the channel. Ionizing radiation reduced the veratridine-stimulated uptake at the earliest times measured (3 and 5 s), when the rate of uptake was greatest. Batrachotoxin-stimulated 22Na+ uptake was less sensitive to inhibition by radiation. The binding of [3H]saxitoxin to its receptor in the sodium channel was unaffected by exposure to ionizing radiation. The effect of ionizing radiation on the lipid order of rat brain synaptic plasma membranes was measured by the fluorescence polarization of the molecular probes 1,6-diphenyl-1,3,5-hexatriene and 1-[4-(trimethylammonium)phenyl]-6-phenyl-1,3,5-hexatriene. A dose of radiation that reduced the veratridine-stimulated uptake of 22Na+ had no effect on the fluorescence polarization of either probe. These results demonstrate an inhibitory effect of ionizing radiation on the voltage-sensitive sodium channels in rat brain synaptosomes. This effect of radiation is not dependent on changes in the order of membrane lipids.

Animals↗

PubMed1985

Intragastric copper sulfate produces a more reliable conditioned taste aversion in vagotomized rats than in intact rats.

Although copper sulfate is an emetic stimulus, preliminary experiments failed to obtain a taste aversion in intact rats following intragastric administration as had been previously reported in the literature. Several experiments were therefore run to further investigate the capacity of intragastric copper sulfate to function as an unconditioned stimulus for taste aversion learning and the role of the vagus in mediating that learning. The results of the first series of experiments showed that intragastric administration of copper sulfate (5 mg/kg X 5H2O) was more effective in reliably producing a taste aversion in vagotomized rats than in sham-operated control rats. The second experiment examined the effects of area postrema lesions on the acquisition of a taste aversion produced by intragastrically administered copper sulfate in vagotomized rats. The results indicated that the taste aversion observed following treatment with intragastric copper sulfate in vagotomized rats could be prevented by lesions of the area postrema. The present results indicate that intragastric administration of copper sulfate is a more reliable unconditioned stimulus for taste aversion learning in vagotomized rats than in intact rats. It is not certain what factors might account for the discrepant results between the present experiments and previously published research.

Animals↗

PubMed1985

Actions of ethanol on voltage-sensitive sodium channels: effects on neurotoxin-stimulated sodium uptake in synaptosomes.

Exposure of rat brain synaptosomes to ethanol in vitro reduced the neurotoxin-stimulated uptake of 22Na+. This effect of ethanol was concentration-dependent, occurred with concentrations of ethanol achieved in vivo and was fully reversible. The inhibitory effect of ethanol on neurotoxin-stimulated sodium uptake was due to a decrease in the maximal effect of the neurotoxins. Ethanol reduced the rate of batrachotoxin-stimulated sodium uptake when measured at 3, 5 and 7 but not 10 or 20 sec after the addition of 22Na+. In a series of aliphatic alcohols, there was a good correlation between potency for inhibition of batrachotoxin-stimulated 22Na+ uptake and the membrane/buffer partition coefficient, suggesting that a hydrophobic site in the membrane was involved in the action of the alcohols. Ethanol did not affect the scorpion venom-induced enhancement of batrachotoxin-stimulated sodium uptake. The inhibitory potency of tetrodotoxin was also unaffected by ethanol. These results demonstrate that ethanol has an inhibitory effect on neurotoxin-stimulated sodium influx occurring in voltage-sensitive sodium channels of brain tissue.

Animals↗

PubMed1985

Characterization of radiation-induced performance decrement using a two-lever shock-avoidance task.

Rats were trained to perform a task involving responses on two levers. Responding on an avoidance lever delayed the onset of electrical footshock for 20 sec and responding on a warning lever turned on a light for 60 sec. When the light was on, the task on the avoidance lever was changed from unsignaled shock avoidance to signaled shock avoidance by preceding the shocks with 5-sec warning tones. The animals preferred the signaled avoidance condition. After 100 Gy of 60Co irradiation, the animals were less able to avoid shock, an effect from which the animals recovered somewhat over 90 min. The response rate on the avoidance lever remained at or above control rates, while the response rate on the warning lever showed an initial increase, followed by a decrease below baseline. The increase in responding on the avoidance lever occurred in bursts just after presentation of the shocks. The data suggest that under these experimental conditions a subject will not respond appropriately to avoid shock or acquire cues that can facilitate the avoidance of shock. The effects, however, do not reflect an inability to perform the required movements but instead appear to reflect some characteristic of the task associated with a particular lever.

Animals↗

PubMed1984

Ethanol inhibits veratridine-stimulated sodium uptake in synaptosomes.

The effects of ethanol and pentobarbital on voltage-sensitive sodium channels in whole brain (rat) synaptosomes were studied using isotopic flux measurements. Incubation of synaptosomes with ethanol or pentobarbital in vitro inhibited veratridine-stimulated 22Na+ uptake. The effect of ethanol is dose-dependent, occurs at sublethal, pharmacologically relevant concentrations and is fully reversible. These results suggest that ethanol and pentobarbital directly interfere with sodium channel function in nervous tissue. Alterations in sodium channel function may be a possible mechanism for the central nervous system (CNS) depressant action of ethanol and related compounds.

Animals↗

PubMed1984

Effects of dose and of partial body ionizing radiation on taste aversion learning in rats with lesions of the area postrema.

The effect of area postrema lesions on the acquisition of a conditioned taste aversion following partial body exposure to ionizing radiation was investigated in rats exposed to head-only irradiation at 100, 200 and 300 rad or to body-only irradiation at 100 and 200 rad. Following head-only irradiation area postrema lesions produced a significant attenuation of the radiation-induced taste aversion at all dose levels, although the rats still showed a significant reduction in sucrose preference. Following body-only exposure, area postrema lesions completely disrupted the acquisition of the conditioned taste aversion. The results are interpreted as indicating that: (a) the acquisition of a conditioned taste aversion following body-only exposure is mediated by the area postrema; and (b) taste aversion learning following radiation exposure to the head-only is mediated by both the area postrema and a mechanism which is independent of the area postrema.

Animals↗

PubMed1984

Recall of a previously acquired conditioned taste aversion in rats following lesions of the area postrema.

A conditioned taste aversion was produced by pairing a novel sucrose solution with either 3 mEq lithium chloride or with 100 rad gamma radiation in rats with the area postrema intact. Lesions of the area postrema were then made in half of the rats exposed to each treatment and in rats that were not treated with the unconditioned stimulus. When tested for a conditioned taste aversion, all treated rats showed a significant aversion to the sucrose solution compared to the untreated control rats. There were no significant differences between rats with area postrema lesions and those with the area postrema intact, indicating that the lesions had no effect on the recall of the previously acquired aversion. The results are interpreted as being consistent with the hypothesis that the role of the area postrema in taste aversion learning is to monitor blood and cerebrospinal fluid for potential toxins and to transmit that information to the central nervous system.

Analysis of Variance↗

PubMed1983

Ionizing radiation decreases veratridine-stimulated uptake of sodium in rat brain synaptosomes.

Veratridine-stimulated uptake of sodium-22 in brain synaptosomes was significantly reduced by ionizing radiation over a dose range of 10 to 1000 rads. The response was dose-dependent and involved a decrease in the maximum effect of veratridine on uptake. The central nervous system may be more sensitive to ionizing radiation than generally thought, perhaps through a loss of the ability of the sodium channel to respond properly to stimulation.

Animals↗

PubMed1983

An automated method for the determination of biogenic amines and their metabolites by high-performance liquid chromatography.

An automated high-performance liquid chromatographic method has been developed that allows for the determination of a number of compounds related to catechol- and indoleamine metabolism. The compounds that can be measured include L-DOPA, dopamine, dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, norepinephrine, 3-methoxy-4-hydroxyphenylglycol, dihydroxyphenylglycol, vanilmandelic acid, epinephrine, 5-hydroxytryptophan, serotonin, 5-hydroxyindoleacetic acid, and 5-hydroxytryptophol. Dihydroxybenzylamine is used as an internal standard. Although dihydroxyphenylglycol and vanilmandelic acid could be detected and quantified, they could not be separated from each other. The method is completely automated and is sensitive enough to detect amounts as low as 500 fmol. Up to 200 samples a week can be analyzed in the automated mode. Using this method, analyses of brain tissue can be accomplished with no need for a cleanup procedure. The value of this procedure lies in its ability to simultaneously determine various amines and metabolites from small tissue samples in the same animals and with automation to analyze a relatively large number of samples a day with little attention by a technician.

Animals↗

PubMed1983

Effects of antiemetics on the acquisition and recall of radiation- and lithium chloride-induced conditioned taste aversions.

A series of experiments were run to evaluate the effect of antiemetics on the acquisition and recall of a conditioned taste aversion induced by exposure to ionizing radiation or by injection of lithium chloride. Groups of male rats were exposed to 100 rad gamma radiation or 3 mEq/kg lithium chloride following consumption of a 10% sucrose solution. They were then injected with saline or with one of three antiemetics (prochlorperazine, trimethobenzamide, or cyclizine) at dose levels that have been reported to be effective in attenuating a previously acquired lithium chloride-induced taste aversion. The pretreatments with antiemetics had no effect on the acquisition or recall of either the lithium chloride- or radiation-induced taste aversion. The data suggest that antiemetics do not disrupt lithium chloride-induced taste aversions as previously reported, nor do they effect radiation-induced taste aversion learning.

Animals↗

PubMed1983

Acquisition of lithium chloride- and radiation-induced taste aversions in hypophysectomized rats.

The effects of hypophysectomy on the acquisition of conditioned taste aversions following injection of lithium chloride and following exposure to ionizing radiation were studied using a two-bottle preference test. Hypophysectomy did not disrupt the acquisition of a taste aversion following either treatment. The results are interpreted as: (a) suggesting that pituitary/adrenal hormones do not mediate the acquisition of a conditioned taste aversion following injections of lithium chloride or following exposure to ionizing radiation in a two-bottle preference test, and (b) consistent with other research suggesting that the involvement of pituitary/adrenal hormones in taste aversion learning may be related to the conflict induced by using a one-bottle test and not to the learning itself.

Animals↗

PubMed1983

The effect of ethanol on GABAergic transmission.

One of the many actions of ethanol involves the GABAergic system. The interaction of ethanol with GABAergic neurons is a complex one involving both presynaptic and postsynaptic sites. Through a presumed fluidization of membranes after a single dose of ethanol, the available in vitro evidence suggests that ethanol disrupts the normal functioning of the GABA-benzodiazepine-chloride ionophore complex in a complicated manner involving a sequential activation of different active sites leading to the facilitation of GABA transmission. This finding has been supported in vivo using electrophysiological techniques. Presynaptic GABAergic neurons may experience a reduced activity, especially at low doses of ethanol. After chronic ethanol treatment, GABAergic transmission may be reduced, especially during an ethanol withdrawal syndrome. Also, other changes in the GABA-benzodiazepine-chloride ionophore complex suggest GABA transmission is suppressed postsynaptically. Drugs which enhance the actions of GABA may be suitable inhibitors of the ethanol withdrawal syndrome. In particular a new class of drugs, the triazolopyridazines, may be promising compounds for treatment of withdrawal with a more specific mode of action and fewer side effects.

Alcohol Withdrawal Delirium↗

PubMed1983

Comparative effects of exposure to high-energy electrons and gamma radiation on active avoidance behaviour.

The effect of two types of ionizing radiation was examined on active avoidance behaviour. Male Sprague-Dawley rats were trained to avoid footshock by jumping onto a retractable ledge. When irradiated with high-energy electrons or gamma photons, their performance was degraded in a dose-dependent manner. However, electrons were 1.6 times as effective as gamma photons with ED50s of 62 and 102 Gy, respectively. All animals recovered within 24 min for all doses used. The data suggest that different types of ionizing radiation may not be equivalent when assessing their effect on behaviour.

Animals↗

PubMed1983

Studies of neurotransmitter interactions after acute and chronic ethanol administration.

Evidence is accumulating suggesting that ethanol has a biphasic effect on several neurotransmitters in the brain and that interactions between two or more transmitters may contribute to the behavioral response obtained after ethanol administration. In the nigrostriatal complex where the most data have been derived, dopaminergic activity responds in a biphasic manner to ethanol treatment. At low doses, dopaminergic activity is elevated, while at high doses, activity is reduced. After chronic ethanol treatment, pre- and postsynaptic dopaminergic activity is hypoactive. Pharmacological data have suggested the possible involvement of acetylcholine (ACh) and gamma-aminobutyric acid (GABA) in the actions of ethanol on the striatal dopaminergic system. In support of this postulate, striatal high-affinity choline uptake, an index of ACh release, is elevated after high doses of ethanol and after ethanol withdrawal. GABA turnover exhibits a biphasic response to ethanol treatment. At low doses of ethanol, GABA turnover is reduced, while at high doses, turnover is unaffected. These latter effects correlate with known interrelationships of these transmitters in the nigrostriatal complex. The data suggest that an action of ethanol on one transmitter may influence the response of another transmitter to ethanol. To further address the interrelationship of transmitters, a high-performance liquid chromatographic method has been developed to study the activity of several transmitters simultaneously. This approach promises to shed more light on this important area.

Acetylcholine↗

PubMed1983

Attenuation of radiation- and drug-induced conditioned taste aversions following area postrema lesions in the rat.

The effects of lesions of the area postrema on the acquisition of radiation- and drug-induced (histamine and lithium chloride) conditioned taste aversions were investigated. The results indicated that area postrema lesions caused a significant attenuation of the aversion produced by pairing a novel sucrose solution with radiation (100 rad) or drug injection. Further, the area postrema lesions produced a similar level of attenuation of the taste aversion in all three treatment conditions. The results are discussed in terms of the implications of this finding for defining the mechanisms by which exposure to ionizing radiation can lead to the acquisition of a conditioned taste aversion.

Animals↗

PubMed1982

Histamine H-1 receptors on rat peritoneal mast cells.

In order to characterize the receptor subtype involved in histamine stimulation of increased cyclic AMP levels in rat mast cells with consequent impairment of anaphylactically induced mediator release, the binding of the H-1 receptor antagonist [3H]pyrilamine to mast cells was examined. Pyrilamine bound rapidly, in a saturable and reversible fashion, and with increased binding at 4 degrees C as compared with 21 degrees C and 37 degrees C. [3H]Pyrilamine binding was displaced by H-1 antagonists (tripelennamine greater than pyrilamine greater than or equal to diphenhydramine) greater than histamine greater than the H-2 antagonist, cimetidine. H-1 agonists displaced pyrilamine binding less efficiently than histamine but better than H-2 agonists. Rat mast cells have a single homogeneous population of low affinity (KD = 222 +/- 33 nM) H-1 receptors with a Bmax of 9.7 +/- 2.3 pm/10(6) mast cells and 5.4 +/- 0.92 x 10(6) binding sites per mast cell. Thus, the mast cell has an H-1 type histamine receptor which is probably involved in histamine-induced cyclic AMP increases.

Aminopyridines↗