Biomedical subjects

W A Hunt

Publications and source records attributed to W A Hunt.

At least 37 records · Page 2Linked to original sources

PubMed1989

Characteristics of radiation-induced performance changes in bar-press avoidance with and without a preshock warning cue.

Rats were trained to perform one of three tasks in which responses on a lever delayed the onset of footshock for 20 sec. One task provided a warning tone beginning 15 sec after the last response on the lever and lasting for 5 sec just prior to the presentation of a shock (fixed-interval signalled avoidance), while a second task provided no external cues (unsignalled avoidance). The third task was similar to the fixed-interval signalled avoidance task, except that the warning tone preceding shock began at varying intervals after the last response on the lever (variable-interval signalled avoidance). Animals trained on the signalled avoidance paradigms received fewer shocks than those on the unsignalled avoidance paradigm. After 10 krads of gamma radiation, animals performing on either task with cues were less able to avoid shock, although they recovered somewhat over a 90-min period. The animals not provided cues also experienced more shocks during the first 10 min after irradiation but were relatively less affected in performing the task. Response rates on the bar and the patterns of responding on these tasks were not significantly different after irradiation, except that animals responded after the onset of shock more often after irradiation than before. These results suggest that rats will continue to effectively use task related cues after irradiation, but that the relative degree of behavioral decrement may depend on the initial level of performance or possibly the complexity of the task.

Animals↗

PubMed1989

Interaction of haloperidol and area postrema lesions in the disruption of amphetamine-induced conditioned taste aversion learning in rats.

Two experiments were run to determine the mechanisms underlying the acquisition of an amphetamine-induced conditioned taste aversion. In the first experiment, it was shown that pretreatment with haloperidol (0.1-0.5 mg/kg, IP) attenuated. but did not prevent, taste aversion learning produced by amphetamine (3 mg/kg, IP). In the second experiment, combining area postrema lesions with haloperidol (0.5 mg/kg) pretreatment completely blocked the acquisition of an amphetamine-induced taste aversion. The results are interpreted as indicating that amphetamine-induced taste aversion learning has both a central component, which is mediated by dopaminergic receptors, and a nondopaminergic peripheral component, which is mediated by the area postrema.

Amphetamine↗

PubMed1989

Behavioral and neurochemical abnormalities after exposure to low doses of high-energy iron particles.

Exposure of rats to high-energy iron particles (600 MeV/amu) has been found to alter behavior after doses as low as 10 rads. The performance of a task that measures upper body strength was significantly degraded after irradiation. In addition, an impairment in the regulation of dopamine release in the caudate nucleus (a motor center in the brain), lasting at least 6 months, was also found and correlated with the performance deficits. A general indication of behavioral toxicity and an index of nausea and emesis, the conditioned taste aversion, was also evident. The sensitivity to iron particles was 10-600 times greater than to gamma photons. These results suggest that behavioral and neurobiological damage may be a consequence of exposure to low doses of heavy particles and that this possibility should be extensively studied.

Animals↗

PubMed1989

An assessment of the behavioral toxicity of high-energy iron particles compared to other qualities of radiation.

Conditioned taste aversion was used to evaluate the behavioral toxicity of exposure to high-energy iron particles (56Fe, 600 MeV/amu) in comparison to that of gamma photons (60Co), high-energy electrons, or fission neutrons. Exposure to high-energy iron particles (5-500 cGy) produced a dose-dependent taste aversion with a maximal effect achieved with a dose of 30 cGy. Gamma photons and electrons were the least effective stimuli for producing a conditioned taste aversion, with a maximal aversion obtained only after exposure to 500 cGy, while the effectiveness of fission neutrons was intermediate to that of photons and iron particles, and a maximal aversion was obtained with a dose of 100 cGy. In the second experiment, rats with lesions of the area postrema were exposed to iron particles (30 cGy), but failed to acquire a taste aversion. The results indicate that (1) high-energy iron particles are more toxic than other qualities of radiation and (2) similar mechanisms mediate the behavioral toxicity of gamma photons and high-energy iron particles.

Animals↗

PubMed1988

Age-related decrements in the muscarinic enhancement of K+-evoked release of endogenous striatal dopamine: an indicator of altered cholinergic-dopaminergic reciprocal inhibitory control in senescence.

Previous experiments have indicated that the release of striatal dopamine (DA) is controlled by inhibitory DA autoreceptors which are mediated by inhibitory cholinergic heteroreceptors (HTRs). Activation of the HTRs by muscarinic or nicotine agonists potentiates the K+-evoked release of DA from the striatum. Present experiments were carried out to determine if this relationship is altered as a function of aging. Cross-cut striatal tissue slices obtained from 3 age-groups (6, 12-18 and 24 months) Wistar rats were superfused with a modified Krebs-Ringer basal release medium containing 2.5 mM KCl. After a 30-min equilibration period, a 5-min baseline fraction was collected from each chamber. The medium was then switched to one containing 30 mM KCl, and depending upon the experiment, 1 of 4 concentrations of a particular muscarinic (oxotremorine, pilocarpine, carbachol or bethanecol) or nicotinic (nicotine) agonist. In some experiments DA autoreceptor function was assessed directly with haloperidol. Six 5-min fractions were taken during depolarization. DA release was assessed using high performance liquid chromatography coupled to electrochemical detection. Results indicated that the efficacy of the muscarinic agonists was reduced in an age-dependent manner with the oldest age groups showing the smallest enhancement. The age at which the decline was seen was dependent on the muscarinic agonist that was applied. Deficits were seen as early as 12 months when full agonists (e.g. carbachol) were applied, but did not appear until 18 months when partial agonists (e.g. oxotremorine) were applied. These age-related alterations were not seen when haloperidol or nicotine were used to enhance the K+-evoked release of DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Alterations in muscarinic control of striatal dopamine autoreceptors in senescence: a deficit at the ligand-muscarinic receptor interface?

Research has indicated that the release of striatal dopamine (DA) is controlled by inhibitory DA autoreceptors which are in turn regulated by inhibitory muscarinic inhibitory cholinergic heteroreceptors (HTRs) located in close vicinity to the autoreceptors. Muscarinic activation enhances K+-evoked release of DA from striatal slices from mature but not senescent rats. Since it has been shown that age-dependent declines in Ca2+ mediated acetylcholine release can be restored by the ionophore A23187, it was of interest to determine if age-related decrements in Ca2+ mobilization might contribute to the alterations in muscarinic control of the striatal DA autoreceptors seen in senescence. Cross-cut striatal tissue slices obtained from two age-groups (6 and 24 months) of Wistar rats were superfused with a modified Krebs-Ringer medium containing 2.5 mM KCl. After a 30-min equilibration period, a 5-min baseline fraction was collected. The medium was then switched to one which contained 30 mM KCl and, depending upon the experiment, the muscarinic agonists carbachol, or oxotremorine or the Ca2+ mobilizing agents A23187 or inositoltrisphosphate (IP3) and enhancement of K+-evoked release of DA was examined. Six 5-min fractions were collected. DA release was determined by HPLC coupled to electrochemical detection. Results indicated that although deficits were seen in oxotremorine and carbachol enhancement of K+-evoked release of DA, these decrements were not observed when either A23187 or IP3 were utilized to enhance the K+-evoked release of DA.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1988

Involvement of histamine H1 and H2 receptors in hypothermia induced by ionizing radiation in guinea pigs.

Radiation-induced hypothermia was examined in guinea pigs. Exposure to the head alone or whole-body irradiation induced hypothermia, whereas exposure of the body alone produced a small insignificant response. Systemic injection of disodium cromoglycate (a mast cell stabilizer) and cimetidine (H2-receptor antagonist) had no effect on radiation-induced hypothermia, whereas systemic and central administration of mepyramine (H1-receptor antagonist) or central administration of disodium cromoglycate or cimetidine attenuated it, indicating the involvement of central histamine through both H1 and H2 receptors in this response. Serotonin is not involved, since the serotonin antagonist methysergide had no effect on radiation-induced hypothermia. These results indicate that central histaminergic systems may be involved in radiation-induced hypothermia.

Animals↗

PubMed1988

Attenuation of a radiation-induced conditioned taste aversion after the development of ethanol tolerance.

An attempt to reduce a radiation-induced conditioned taste aversion (CTA) was undertaken by rendering animals tolerant to ethanol. Ethanol tolerance, developed over 5 days, was sufficient to block a radiation-induced taste aversion, as well as an ethanol-induced CTA. Several intermittent doses of ethanol, which did not induce tolerance but removed the novelty of the conditioning stimulus, blocked an ethanol-induced CTA but not the radiation-induced CTA. A CTA induced by doses of radiation up to 500 rads was attenuated. These data suggest that radioprotection developing in association with ethanol tolerance is a result of a physiological response to the chronic presence of ethanol not to the ethanol itself.

Animals↗

PubMed1988

Radiation-induced increases in sensitivity of cataleptic behavior to haloperidol: possible involvement of prostaglandins.

The effects of radiation exposure on haloperidol-induced catalepsy were examined in order to determine whether elevated prostaglandins, through an action on dopaminergic autoreceptors, could be involved in the radiation-induced increase in the potency of this neuroleptic. Cataleptic behavior was examined in animals irradiated with various doses of gamma photons (1-150 Gy) and pretreated with a subthreshold dose of haloperidol (0.1 mg/kg). This approach was chosen to maximize any synergistic effects of radiation and haloperidol. After irradiation with doses less than or equal to 30 Gy, the combined treatment of haloperidol and radiation produced catalepsy, whereas neither treatment alone had an effect. This observed catalepsy could be blocked with prior administration of indomethacin, a prostaglandin synthesis inhibitor. Animals exposed to doses of radiation less than or equal to 50 Gy and no haloperidol, however, displayed apparent catalepsy. This effect was also antagonized by indomethacin. Prostaglandins can induce catalepsy and when administered in subthreshold doses along with subthreshold doses of haloperidol, catalepsy was observed. In order to assess a possible action of prostaglandins and radiation on dopaminergic activity, the functioning of striatal dopaminergic autoreceptors was examined by determining the effects of varying concentrations of haloperidol on the K+-evoked release of dopamine from striatal slices obtained from parallel groups of animals treated as above. Results indicated that sensitivity to haloperidol increased (higher K+-evoked dopamine release) in slices from irradiated or prostaglandin-treated animals and that this increase in sensitivity was blocked by indomethacin. Results from both experiments suggest that radiation-induced increases in endogenous neuronal mediators, such as prostaglandins, can induce catalepsy through an action on dopaminergic autoreceptors.

Animals↗

PubMed1988

Attenuation and cross-attenuation in taste aversion learning in the rat: studies with ionizing radiation, lithium chloride and ethanol.

The preexposure paradigm was utilized to evaluate the similarity of ionizing radiation, lithium chloride and ethanol as unconditioned stimuli for the acquisition of a conditioned taste aversion. Three unpaired preexposures to lithium chloride (3.0 mEq/kg, IP) blocked the acquisition of a taste aversion when a novel sucrose solution was paired with either the injection of the same dose of lithium chloride or exposure to ionizing radiation (100 rad). Similar pretreatment with radiation blocked the acquisition of a radiation-induced aversion, but had no effect on taste aversions produced by lithium chloride (3.0 or 1.5 mEq/kg). Preexposure to ethanol (4 g/kg, PO) disrupted the acquisition of an ethanol-induced taste aversion, but not radiation- or lithium chloride-induced aversions. In contrast, preexposure to either radiation or lithium chloride attenuated an ethanol-induced taste aversion in intact rats, but not in rats with lesions of the area postrema. The results are discussed in terms of relationships between these three unconditioned stimuli and in terms of implications of these results for understanding the nature of the proximal unconditioned stimulus in taste aversion learning.

Animals↗

PubMed1988

Opposite effects of WR-2721 and WR-1065 on radiation-induced hypothermia: possible correlation with oxygen uptake.

Ionizing radiation induces hypothermia in guinea pigs. While systemic injection of the radioprotectant S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) did not block hyperthermia induced by exposure to 10 Gy of gamma radiation, central administration did attenuate it. The dephosphorylated metabolite of WR-2721, N-(2-mercaptoethyl)-1,3-diaminopropane (WR-1065), accentuated radiation-induced hypothermia by both routes of administration. In brain homogenates, oxygen uptake was inhibited by WR-2721 but elevated by WR-1065. These results suggest that the antagonism of radiation-induced hypothermia found only after central administration of WR-2721 is due to its direct actions and not to its dephosphorylated metabolite and that this effect may be correlated with the inhibition by WR-2721 of oxygen uptake.

Amifostine↗

PubMed1988

Implication of prostaglandins and histamine H1 and H2 receptors in radiation-induced temperature responses of rats.

Exposure of rats to 1-15 Gy gamma radiation (60Co) induced hyperthermia, whereas 20-200 Gy induced hypothermia. Exposure either to the head or to the whole body to 10 Gy induced hyperthermia, while body-only exposure produced hypothermia. This observation indicates that radiation-induced fever is a result of a direct effect on the brain. The hyperthermia due to 10 Gy was significantly attenuated by the pre- or post-treatment with a cyclooxygenase inhibitor, indomethacin. Hyperthermia was also altered by the central administration of a mu-receptor antagonist naloxone but only at low doses of radiation. These findings suggest that radiation-induced hyperthermia may be mediated through the synthesis and release of prostaglandins in the brain and to a lesser extent to the release of endogenous opioid peptides. The release of histamine acting on H1 and H2 receptors may be involved in radiation-induced hypothermia, since both the H1 receptor antagonist, mepyramine, and H2 receptor antagonist, cimetidine, antagonized the hypothermia. The results of these studies suggest that the release of neurohumoral substances induced by exposure to ionizing radiation is dose dependent and has different consequences on physiological processes such as the regulation of body temperature. Furthermore, the antagonism of radiation-induced hyperthermia by indomethacin may have potential therapeutic implications in the treatment of fever resulting from accidental irradiations.

Animals↗

PubMed1987

Effects of ethanol on the functional properties of sodium channels in brain synaptosomes.

Voltage-sensitive sodium channels in excitable cell membranes are responsible for the rapid increase in permeability to sodium ions that occurs during depolarization. Neurotoxins that bind with high affinity and specificity to voltage-sensitive sodium channels have been widely used to identify and characterize the structure and function of sodium channels in nerve and skeletal muscle. This chapter describes the actions of ethanol on the functional properties of voltage-sensitive sodium channels in mammalian brain nerve endings. The effects of acute and chronic ethanol administration are also reviewed. Alterations in the function of neuronal membrane sodium channels may be involved in the depressant effect of ethanol.

Animals↗

PubMed1987

Taste aversion learning produced by combined treatment with subthreshold radiation and lithium chloride.

These experiments were designed to determine whether treatment with two subthreshold doses of radiation or lithium chloride, either alone or in combination, could lead to taste aversion learning. The first experiment determined the thresholds for a radiation-induced taste aversion at 15-20 rad and for lithium chloride at 0.30-0.45 mEq/kg. In the second experiment it was shown that exposing rats to two doses of 15 rad separated by up to 3 hr produced a taste aversion. Treatment with two injections of lithium chloride (0.30 mEq/kg) did not produce a significant reduction in preference. Combined treatment with radiation and lithium chloride did produce a taste aversion when the two treatments were administered within 1 hr of each other. The results are discussed in terms of the implications of these findings for understanding the nature of the unconditioned stimuli leading to the acquisition of a conditioned taste aversion.

Animals↗

PubMed1987

Interactions between radiation and amphetamine in taste aversion learning and the role of the area postrema in amphetamine-induced conditioned taste aversions.

Three experiments were run to assess the role of the area postrema in taste aversion learning resulting from combined treatment with subthreshold unconditioned stimuli and in the acquisition of an amphetamine-induced taste aversion. In the first experiment, it was shown that combined treatment with subthreshold radiation (15 rad) and subthreshold amphetamine (0.5 mg/kg, IP) resulted in the acquisition of a taste aversion. The second experiment showed that lesions of the area postrema blocked taste aversion learning produced by two subthreshold doses of amphetamine. In the third experiment, which looked at the dose-response curve for amphetamine-induced taste aversion learning in intact rats and rats with area postrema lesions, it was shown that both groups of rats acquired taste aversions following injection of amphetamine, although the rats with lesions showed a less severe aversion than the intact rats. The results are interpreted as indicating that amphetamine-induced taste aversion learning may involve area postrema-mediated mechanisms, particularly at the lower doses, but that an intact area postrema is not a necessary condition for the acquisition of an amphetamine-induced taste aversion.

Amifostine↗

PubMed1987

Actions of ethanol on voltage-sensitive sodium channels: effects on neurotoxin binding.

Exposure of rat forebrain synaptosomes (P2) to ethanol in vitro reduced the specific binding of [3H]batrachotoxinin A 20-alpha-benzoate ([3H]BTX-B) to voltage-sensitive sodium channels. This effect of ethanol was concentration-dependent and was affected by the membrane potential. Under depolarizing conditions ethanol was significantly more potent at inhibiting [3H]BTX-B binding. Scatchard analysis of [3H]BTX-B binding revealed that ethanol increased the equilibrium binding constant without affecting the apparent maximum number of binding sites. The rate of formation of the [3H]BTX-B/receptor complex was unchanged in the presence of ethanol whereas the rate of dissociation was accelerated by ethanol. These findings are consistent with an indirect allosteric mechanism for inhibition of [3H]BTX-B binding. The binding of [3H]saxitoxin was unaffected by ethanol suggesting that the specific receptor sites in the channel display differential sensitivity to the inhibitory effect of ethanol. These data, in conjunction with ion flux measurements, provide further evidence that ethanol can affect the voltage-sensitive sodium channels in neuronal membranes.

Animals↗

PubMed1987

Actions of ethanol on voltage-sensitive sodium channels: effects of acute and chronic ethanol treatment.

The effects of acute and chronic ethanol treatment on neurotoxin-stimulated 22Na+ uptake and [3H]batrachotoxinin A20-alpha-benzoate binding to neuronal sodium channels were studied in rat forebrain synaptosomes. Fluorescence measurements were used to assess the intrinsic order or fluidity and the sensitivity to ethanol of rat forebrain synaptic plasma membranes at various intervals during and after chronic ethanol treatment. Acute ethanol administration had no significant effect on neurotoxin binding in the absence or presence of ethanol in vitro or on sodium uptake in the absence of ethanol in vitro. However, a single dose of ethanol produced a dose and time-dependent attenuation of the inhibitory effect of ethanol on sodium uptake, suggestive of acute tolerance. Chronic ethanol treatment reduced the influx of 22Na+ in the presence of batrachotoxin and diminished the inhibitory effect of ethanol in vitro on sodium uptake for up to 20 days after withdrawal, but the specific binding of the neurotoxin in the presence or absence of ethanol was unchanged. Synaptic plasma membranes from chronic ethanol-treated rats showed no change in intrinsic order but the disordering effect of ethanol was significantly smaller for up to 20 days after withdrawal. Results of this study demonstrate that brain tissue from ethanol-treated rats can adapt rapidly to some effects of ethanol and that chronic ethanol administration can reduce the effects of ethanol on physical and functional properties of neurons for a prolonged period of time.

Animals↗

PubMed1986

Role of the area postrema in radiation-induced taste aversion learning and emesis in cats.

The role of the area postrema in radiation-induced emesis and taste aversion learning and the relationship between these behaviors were studied in cats. The potential involvement of neural factors which might be independent of the area postrema was minimized by using low levels of ionizing radiation (100 rads at a dose rate of 40 rads/min) to elicit a taste aversion, and by using body-only exposures (4500 and 6000 rads at 450 rads/min) to produce emesis. Lesions of the area postrema disrupted both taste aversion learning and emesis following irradiation. These results, which indicate that the area postrema is involved in the mediation of both radiation-induced emesis and taste aversion learning in cats under these experimental conditions, are interpreted as being consistent with the hypotheses that similar mechanisms mediate both responses to exposure to ionizing radiation, and that the taste aversion learning paradigm can therefore serve as a model system for studying radiation-induced emesis.

Animals↗