Biomedical subjects

B M Rabin

Publications and source records attributed to B M Rabin.

At least 37 records · Page 2Linked to original sources

PubMed1996

Free radicals and taste aversion learning in the rat: nitric oxide, radiation and dopamine.

1. Injection of sodium nitroprusside (SNP) or N-tert-butyl-alpha-phenyl nitrone (PBN) produces a conditioned taste aversion (CTA) in rats. The CTA can be prevented by pretreatment with N omega-nitro-L-arginine (L-NArg), indicating that nitric oxide (NO) is a behaviorally toxic compound. 2. Radiation-induced CTA learning is not affect by pretreatment with L-NArg or by preexposure to PBN, indicating that a radiation-stimulated formation of NO does not mediate the toxic effects of radiation on behavior. 4. Pretreating rats with the dopamine antagonist haloperidol prevented the acquisition of the CTA produced by SNP and attenuated, but did not eliminate, the PBN-induced CTA. Preexposure to the dopamine agonist amphetamine, attenuated a PBN-induced CTA, although PBN preexposure did not affect an amphetamine-induced CTA. 5. The results are interpreted as supporting a role for NO-stimulated dopamine release in the acquisition of taste aversions following injection of SNP or PBN.

Animals↗

PubMed1996

Radiation-induced changes in the central nervous system and head and neck.

Radiation therapy of the brain, neck, and spine can be associated with radiation-induced changes that are increasingly evident radiologically. These changes affect the central nervous system (focal necrosis, diffuse white matter injury, atrophy, mineralizing microangiopathy, telangiectasia, optic neuropathy, large vessel vasculopathy), bone (fatty replacement of marrow, osteoradionecrosis, sinus inflammation), and superficial and deep soft tissues and include neoplasia. Focal necrosis, which most commonly occurs at the treatment site, is seen at computed tomography (CT) and magnetic resonance (MR) imaging as a ring-enhancing mass with edema and mass effect, findings similar to those of tumor recurrence. Diffuse white matter injury appears as hypoattenuating (at CT) or hyperintense (at MR imaging) small foci near the frontal or occipital horns or as a confluent band extending from the ventricles to the corticomedullary junction. Fatty replacement of marrow is the most common osseous complication seen on MR images. Osteoradionecrosis, which occurs most often in the mandible, appears as a focal lytic area at CT and with abnormal marrow signal and cortical destruction at MR imaging. The most common changes in the superficial soft tissues of the head and neck, edema and fibrosis, are seen radiologically as skin thickening and increased soft-tissue attenuation with stranding of subcutaneous fat. Meningioma, the most common radiation-induced CNS tumor, can be distinguished from spontaneous meningiomas on the basis of clinical characteristics (eg, presence of focal alopecia and scalp atrophy).

Adolescent↗

PubMed1994

Behavioral endpoints for radiation injury.

The relative behavioral effectiveness of heavy particles was evaluated. Using the taste aversion paradigm in rats, the behavioral toxicity of most types of radiation (including 20Ne and 40Ar) was similar to that of 60Co photons. Only 56Fe and 93Nb particles and fission neutrons were significantly more effective. Using emesis in ferrets as the behavioral endpoint, 56Fe particles and neutrons were again the most effective; however, 60Co photons were significantly more effective than 18 MeV electrons. These results suggest that LET does not completely predict behavioral effectiveness. Additionally, exposing rats to 10 cGy of 56Fe particles attenuated amphetamine-induced taste aversion learning. This behavior is one of a broad class of behaviors which depends on the integrity of the dopaminergic system and suggests the possibility of alterations in these behaviors following exposure to heavy particles in a space radiation environment.

Amphetamine↗

PubMed1994

Iron-56 irradiation diminishes muscarinic but not alpha 1-adrenergic-stimulated low-Km GTPase in rat brain.

Initial findings from our laboratory have indicated that muscarinic enhancement of K(+)-evoked release of dopamine from perifused striatal slices is reduced after exposure to 56Fe-particle irradiation. This finding suggested that there is a radiation-induced deficit in muscarinic receptor sensitivity. Subsequent findings have indicated that at least part of the loss in sensitivity may occur as a result of alterations in the initial steps of the signal transduction process and involve muscarinic receptor-G protein coupling/uncoupling. The present study was carried out to localize this deficit further by determining carbachol-stimulated low-Km guanosine triphosphatase (GTPase) activity in striatal and hippocampal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of 56Fe-particle irradiation. In addition, to examine the specificity of the effect of 56Fe-particle irradiation, alpha 1-adrenergic-stimulated low-Km GTPase activity was also examined in these tissues. The results showed that there was a high degree of specificity in the effects of 56Fe particles. Decrements were observed in muscarinic-stimulated low-Km GTPase in striatum but not in hippocampus, and 56Fe-particle irradiation did not affect alpha 1-adrenergic low-Km GTPase activity in either brain tissue.

Animals↗

PubMed1994

Reductions of 56Fe heavy-particle irradiation-induced deficits in striatal muscarinic receptor sensitivity by selective cross-activation/inhibition of second-messenger systems.

Recent experiments have revealed radiation-induced (600 MeV/u 56Fe energetic particles) losses of sensitivity of rodent neostriatal muscarinic receptors to stimulation by cholinergic agonists that appears as reductions in oxotremorine enhancement of K(+)-evoked dopamine release. These losses were postulated to be the result of radiation-induced alterations early in phosphoinositide-mediated signal transduction. Additional findings indicated that if the ligand-receptor-G protein interface was by passed no radiation deficits were seen. In the present study, radiation-induced deficits in K(+)-evoked dopamine release were examined in perifused striatal tissue obtained from rats exposed to 0, 0.1 or 1.0 Gy of 56Fe particles (600 MeV/u). Results showed that these deficits could be reduced by co-applying combinations of various pharmacological agents that were known to have differential effects on various second messengers such as 1,4,5-inositol-trisphosphate (IP3). Combinations included oxotremorine-carbachol, and either oxotremorine or carbachol with arginine vasopressin or arachidonic acid. These results are discussed in terms of putative radiation-induced changes in receptor-containing membranes which alter receptor-G protein coupling/uncoupling.

Analysis of Variance↗

PubMed1994

Exposure to heavy charged particles affects thermoregulation in rats.

Rats exposed to 0.1-5 Gy of heavy particles (56Fe, 40Ar, 20Ne or 4He) showed dose-dependent changes in body temperature. Lower doses of all particles produced hyperthermia, and higher doses of 20Ne and 56Fe produced hypothermia. Of the four HZE particles, 56Fe particles were the most potent and 4He particles were the least potent in producing changes in thermoregulation. The 20Ne and 40Ar particles produced an intermediate level of change in body temperature. Significantly greater hyperthermia was produced by exposure to 1 Gy of 20Ne, 40Ar and 56Fe particles than by exposure to 1 Gy of 60Co gamma rays. Pretreating rats with the cyclo-oxygenase inhibitor indomethacin attenuated the hyperthermia produced by exposure to 1 Gy of 56Fe particles, indicating that prostaglandins mediate 56Fe-particle-induced hyperthermia. The hypothermia produced by exposure to 5 Gy of 56Fe particles is mediated by histamine and can be attenuated by treatment with the antihistamines mepyramine and cimetidine.

Alpha Particles↗

PubMed1993

Deficits in the sensitivity of striatal muscarinic receptors induced by 56Fe heavy-particle irradiation: further "age-radiation" parallels.

We had previously shown that there was a loss of sensitivity of muscarinic receptors (mAChR) to stimulation by cholinergic agonists (as assessed by examining oxotremorine enhancement of K(+)-evoked release of dopamine from neostriatal slices) in animals that had been exposed to energetic particles (56Fe, 600 MeV/n), an important component of cosmic rays. This loss of mAChR sensitivity was postulated to be the result of radiation-induced alterations in phosphoinositide-mediated signal transduction. The present experiments were undertaken as a first step toward determining the locus of these radiation-induced deficits in signal transduction by examining K+ enhancement of release of dopamine in 56Fe-exposed animals (0, 0.1, and 1.0 Gy) with agents [A23187, a potent Ca2+ ionophore, or 1,4,5-inositol trisphosphate (IP3)] that "bypass" the mAChR-G protein interface and by comparing the response to oxotremorine-enhanced K(+)-evoked release of dopamine. Results showed that although oxotremorine-enhanced K(+)-evoked release of dopamine was reduced significantly in the radiation groups, no radiation effects were seen when A23187 or IP3 was used to enhance K(+)-evoked release of dopamine. Since similar findings have been observed in aging, the results are discussed in terms of the parallels between aging and radiation effects in signal transduction that might exist in the neostriatum.

Aging↗

PubMed1992

Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine.

The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.

Amphetamine↗

PubMed1992

Emesis in ferrets following exposure to different types of radiation: a dose-response study.

Ferrets were exposed to gamma rays (60Co), fission neutrons, high-energy electrons (18.5 MeV) or iron particles (56Fe, 600 MeV/amu) in order to establish the dose-response relationships for emesis following exposure to different types of radiation. The results showed that the mean effective doses (ED50s) for iron particles (35 cGy) and neutrons (40 cGy) were similar. High-energy electrons were the least effective radiation, with an ED50 of 138 cGy. Gamma rays, with an ED50 of 95 cGy, showed an intermediate effectiveness. The results suggest that the relative effectiveness of different types of radiation generally increases with an increase in linear energy transfer (LET), although LET is not completely predictive of relative behavioral effectiveness.

Animals↗

PubMed1992

Possible "accelerated striatal aging" induced by 56Fe heavy-particle irradiation: implications for manned space flights.

The present experiments were carried out to determine the effects of energy deposition from energetic iron (56Fe particles, an important component of cosmic rays) on motor behavioral performance and to determine if the observed deficits were caused by alterations in the neostriatum (an important motor control area). Neostriatal function was assessed with two correlated parameters, i.e., motor behavioral performance (wire suspension task), and oxotremorine-enhanced K(+)-evoked release of dopamine from perifused striatal slices. Rats were exposed to one of several doses of 56Fe-particle irradiation (0.10-1.0 Gy) and tested on a wire suspension task at 3-180 days postirradiation. Results indicated that profound decrements occurred in both of these indices. The effects on K(+)-evoked release of dopamine were evident for as long as 180 days after irradiation, and a subsequent experiment indicated that these effects appeared as early as 12 h postirradiation. Since similar findings have been observed in aged rats, the results are discussed in terms of these particles producing a possible accelerated striatal aging effect.

Aging↗

PubMed1991

Relationship between linear energy transfer and behavioral toxicity in rats following exposure to protons and heavy particles.

Rats were exposed to protons (155 MeV) or to helium (165 MeV/amu), neon (522 MeV/amu) or argon (670 MeV/amu) particles to evaluate the behavioral toxicity of these types of radiations. Behavioral toxicity was assessed using the conditioned taste aversion paradigm. Exposure to all types of radiation produced dose-dependent increases in the intensity of the acquired taste aversion. However, the intensity of the aversions, measured as the dose that produced a 50% decrease in the intake of the sucrose-conditioned stimulus, did not show significant variation as a function of the linear energy transfer (LET) of the radiation. The results are discussed in terms of the relationship between LET and behavioral toxicity.

Animals↗

PubMed1990

Reduction of 3-methoxytyramine concentrations in the caudate nucleus of rats after exposure to high-energy iron particles: evidence for deficits in dopaminergic neurons.

Exposure to low doses of high-energy iron particles can alter motor behavior. The ability of rats to hang from a wire has been reported to be significantly degraded after exposure to doses as low as 0.5 Gy. In addition, deficits in the ability of acetylcholine to regulate dopamine release in the caudate nucleus (an area in the brain important for motor function) have been found. The concentrations of 3-methoxytyramine (3-MT), a metabolite of dopamine whose concentrations reflect dopamine release in vivo, were measured after rats were exposed to different doses of high-energy iron particles to gain further information about the effect of radiation on the dopaminergic system. Concentrations of 3-MT were significantly reduced 3 days after exposure to 5 Gy but returned to control values by 8 days. After 6 months, concentrations were again less than control values. Exposure to 5 Gy of high-energy electrons or gamma photons had no effect 3 days after exposure. Very high doses of electrons were needed to alter 3-MT concentrations. One hundred grays of electrons decreased 3-MT 30 min after irradiation but levels returned to control values by 60 min. Gamma photons had no effect after doses up to 200 Gy. These results provide further evidence that exposure to heavy particles can degrade motor behavior through an action on dopaminergic mechanisms and that this can occur after doses much lower than those needed for low-LET radiation.

3,4-Dihydroxyphenylacetic Acid↗

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

Preparation and care of the area postrema-lesioned cat.

The area postrema (AP) is being widely studied to delineate its role in such varied functions as blood pressure regulation, conditioned taste aversion, water and energy balance, and radiation-induced emesis. This paper describes the preoperative preparation, surgical procedure, and postoperative care of cats kept long-term in which the AP was lesioned by electrocautery. A dorsal midline approach under gas anesthesia allowed access to selectively lesion the AP. Cats fully regained consciousness the same day and many became homeostatic within 24-48 h. Results of experiments using this model demonstrate the usefulness and effectiveness of the technique for model preparation.

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

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

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↗