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M R Landauer

Publications and source records attributed to M R Landauer.

At least 37 records · Page 2Linked to original sources
PubMed1990

Advances in radioprotection through the use of combined agent regimens.

The most effective radioprotective agents exhibit toxicities that can limit their usefulness. It may be possible to use combinations of agents with different radioprotective mechanisms of action at less toxic doses, or to reduce the toxicity of the major protective compound by adding another agent. With regard to the latter possibility, improved radioprotection and reduced lethal toxicity of the phosphorothioate WR-2721 was observed when it was administered in combination with metals (selenium, zinc or copper). The known mechanisms of action of potential radioprotective agents and varying effects of different doses and times of administration in relation to radiation exposure must be considered when using combined-agent regimens. A number of receptor-mediated protectors and other biological compounds, including endotoxin, eicosanoids and cytokines, have at least an additive effect when administered with thiol protectors. Eicosanoids and other bioactive lipids must be administered before radiation exposure, whereas some immunomodulators have activity when administered either before or after radiation exposure. For example, the cytokine interleukin-1 administered simultaneously with WR-2721 before irradiation or after irradiation enhances the radioprotective efficacy of WR-2721. The most effective single agents or combinations of protectors result in a decrement in locomotor activity, an index of behavioral toxicity. Recent evidence indicates that administration of the CNS stimulant caffeine mitigates the behavioral toxicity of an effective radioprotective dose of the phosphorothioate WR-3689 without altering its radioprotective efficacy. These examples indicate that the use of combinations of agents is a promising approach for maximizing radioprotection with minimal adverse effects.

Animals↗
PubMed1990

Onset of behavioral effects in mice exposed to 10 Gy 60Co radiation.

The effects of 10 Gray (Gy) 60 Co radiation on social behavior, locomotor activity, and body weight were assessed in individually housed male Swiss-Webster mice. In Experiment 1, aggressive behavior was evaluated prior to irradiation and for 7 d postirradiation by placing an untreated intruder in the irradiated or sham-irradiated resident's home cage for 5 min. Offensive aggressive behavior was not affected significantly by radiation until day 7 postirradiation, when attack latency increased, the frequency and duration of fighting decreased, and the frequency of bites, lunges, and chases decreased. Untreated intruder mice paired with irradiated resident mice showed a decrease in the duration of defensive upright postures and a decrease in the frequency of defensive upright postures, squeaks, and escapes on day 7 postirradiation. In Experiment 2, locomotor activity and body weight were monitored for 7 d postirradiation. Body weight was decreased in irradiated mice beginning 4 d postirradiation. Locomotor activity was suppressed in irradiated animals 90 min after irradiation and remained depressed throughout the 7-d testing period.

Aggression↗
PubMed1990

Effects of zacopride and BMY25801 (batanopride) on radiation-induced emesis and locomotor behavior in the ferret.

The antiemetic and locomotor effects of two substituted benzamides, zacopride and batanopride (BMY25801), were compared in ferrets after bilateral 60Co irradiation at 2, 4 or 6 Gy. Both zacopride and BMY25801 were effective against emesis and related signs. Zacopride, tested at several doses (0.003, 0.03 and 0.3 mg/kg), appeared to be more potent because it abolished emesis at 100-fold lower doses than did BMY25801 (3 mg/kg). The ED50 value for the antiemetic effect of zacopride was 0.026 mg/kg (confidence levels = 0.0095, 0.072 mg/kg). However, analysis of emetic parameters recorded from vomiting animals (e.g., latency to first emesis) demonstrated that BMY25801 provided greater antiemetic protection in this population than zacopride without any apparent side effects. Locomotor activity was significantly depressed by both radiation (all doses) and zacopride alone (0.03 mg/kg and 0.3 mg/kg). BMY25801 alone did not affect locomotor activity, and protected against the radiation-induced locomotor decrement. Although zacopride potentiated the locomotor decrement to radiation, no clear dose-response relationship was evident. Bilateral abdominal vagotomy significantly increased the latency to the first emetic episode and significantly reduced the number of retches, but did not alter the duration of the prodromal response to 4-Gy irradiation. Unilateral vagotomies had no effect. Zacopride (at 0.03 mg/kg and 0.3 mg/kg) remained an effective antiemetic in animals that received a bilateral vagotomy, abolishing emesis in four of eight and two of eight ferrets, respectively. These data suggest that the antiemetic action of zacopride does not fully depend on intact vagal innervation and also acts via other pathways.

Animals↗
PubMed1989

Effect of electron radiation on aggressive behavior, activity, and hemopoiesis in mice.

The behavioral and physiological effects of 10 Gray (Gy) LINAC electrons in male Swiss-Webster mice were followed for 12 days postirradiation (PR). In Experiment 1, aggressive behavior was assessed in irradiated or sham-irradiated resident mice using a resident-intruder paradigm. Aggressive offensive behavior in the irradiated residents was significantly decreased beginning 2 to 5 days PR, and remained suppressed. Defensive behavior in the nonirradiated intruders was decreased significantly by day 5 PR. In Experiment 2, spontaneous locomotor activity was monitored. Ambulation of irradiated mice was significantly depressed from day 5 PR on, while rearing was affected as early as day 2 PR and remained suppressed. Body weights of irradiated animals were significantly decreased by 5 days PR. In Experiment 3, blood parameters were examined. Compared to sham-irradiated controls, leukocytes, erythrocytes, and hematocrit of irradiated mice were reduced significantly beginning on day 1 PR and remained suppressed, while platelets and hemoglobin were decreased beginning day 2 PR. These results demonstrate that 10 Gy of high-energy electrons results in earlier behavioral deficits than has been observed previously with the same dose of gamma photons.

Aggression↗
PubMed1989

Effects of acute sublethal gamma radiation exposure on aggressive behavior in male mice: a dose-response study.

The resident-intruder paradigm was used to assess the effects of gamma radiation (0, 3, 5, 7 Gray [Gy] cobalt-60) on aggressive offensive behavior in resident male mice over a 3-month period. The defensive behavior of nonirradiated intruder mice was also monitored. A dose of 3 Gy had no effect on either the residents' offensive behavior or the defensive behavior of the intruders paired with them. Doses of 5 and 7 Gy produced decreases in offensive behavior of irradiated residents during the second week postirradiation. The nonirradiated intruders paired with these animals displayed decreases in defensive behavior during this time period, indicating a sensitivity to changes in the residents' behavior. After the third week postirradiation, offensive and defensive behavior did not differ significantly between irradiated mice and sham-irradiated controls. This study suggests that sublethal doses of radiation can temporarily suppress aggressive behavior but have no apparent permanent effect on that behavior.

Aggression↗
PubMed1988

Long-term effects of radioprotector WR-2721 on locomotor activity and body weight of mice following exposure to ionizing radiation.

The effects of 13 Gy gamma-radiation alone and in combination with 200 mg/kg of the radioprotector S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) on locomotor activity and body weight were examined in CD2F1 mice over a 10-month period. The results confirmed that WR-2721 is an excellent radioprotector against lethality. All mice receiving 13 Gy without WR-2721 died in 5-7 days. For mice that received WR-2721 alone or WR-2721 + radiation, survival at 30 days was 100% and 70%, respectively. Body weights of mice receiving WR-2721 without radiation were comparable to control animals. Body weights of animals given WR-2721 + radiation fell on days 1-5 and then increased until day 11, but remained below control values throughout the experiment. Animals in the radiation-only group did not exhibit any significant reductions in behavior until day 2 post-irradiation. Mice administered WR-2721 alone showed significantly reduced locomotor activity levels on day 0 then completely recovered within 24 h and exhibited normal body weights. Animals given WR-2721 before irradiation showed greater reductions in locomotor activity on day 0 than either the WR-2721 or radiation-only groups and recovered to control level by day 3. Beginning on day 5, they showed significant reductions in activity. Mice pretreated with WR-2721 that survived a normally lethal dose of radiation showed a 20-40% reduction in locomotor performance that recovered in 2-5 months.

Amifostine↗
PubMed1987

Acute inhalation toxicity of 3,3-dimethyl-2-butanol in Sprague-Dawley rats.

Sprague-Dawley rats were given 15, 70 and 140 min exposures to 15 mg/l 3,3-dimethyl-2-butanol, pinacolyl alcohol (PA), or 6-hour exposures to 0.2, 1.0 and 5.0 mg/l PA (1 mg/l = 240 ppm). A 50% mortality rate was obtained at the longest exposure to 15 mg/l. Sex related differences in the blood levels of PA and pinacolone were noted, and the surviving male rats failed to gain weight normally in the first week after exposure. In rats exposed to 5.0 mg/l for 6 hours, there were reductions in horizontal and vertical activity and the minute volume was 55% of controls at the end of exposure. Like many secondary alcohols, PA poses only a possible inhalation hazard; however, male rats may be somewhat more susceptible than females.

Administration, Inhalation↗
PubMed1987

Dose and time relationships of the radioprotector WR-2721 on locomotor activity in mice.

The effects of the radioprotector S-2-(3-aminopropylamino)ethylphosphorothioic acid (WR-2721) on locomotor activity were evaluated in CD2F1 male mice. Separate groups of animals (N = 10/group) received an IP injection of vehicle, 25, 50, 100, 200, or 400 mg/kg of WR-2721 immediately before testing. Horizontal and vertical activity were measured using a Digiscan automated animal activity monitor. The latency to onset and duration of action of each dose of the radioprotector were recorded. For both behavioral measures, a significant reduction was observed in activity at doses of 200 and 400 mg/kg. A dose of 200 mg/kg had a 12- to 14-min latency to onset and significantly reduced behavioral activity for 3 hr. Mice injected with 400 mg/kg exhibited locomotor deficits within 8-10 min and were affected for up to 9 hr. The ED50 for horizontal and vertical activities at 1 hr postinjection were determined to be 271 and 105 mg/kg, respectively. The results demonstrate that significant reductions in locomotor activity are exhibited at doses of 200 mg/kg or more and that vertical activity was more sensitive to the disruptive effects of WR-2721 than was horizontal activity.

Amifostine↗
PubMed1987

Locomotor behavior in mice following exposure to fission-neutron irradiation and trauma.

Locomotor activity, body weights, and food and water consumption were monitored in female mice for 35 d following a sublethal wound (W), burn (B), exposure to 3 Gray fission neutron radiation (R), or combination of these injuries: radiation-wound (RW) and radiation-burn (RB). Activity in groups W and RW was depressed immediately after injury, with recovery to control levels after 5 and 14 d, respectively. Mice that received radiation alone showed a biphasic response with decrements in activity on days 0-4 and 9-11. Groups B and RB exhibited depressed activity levels that differed significantly from control levels until day 17. Food intake was reduced for about 6 d in groups R, W, RW, and RB. Body weights decreased for 4 d in groups R, W, RW, and RB, but returned to control levels by the end of the experiment. Animals in group B did not show significant reduction in food intake or body weight. Water consumption was reduced for 5-6 d in groups R and RB and was increased in groups W, RW, and B. The data suggest that behavioral responses to fission-neutron radiation are exacerbated by tissue trauma.

Animals↗
PubMed1986

Effects of the organophosphorus compound, O-ethyl-N-dimethyl-phosphoramidocyanidate (tabun), on flavor aversions, locomotor activity, and rotarod performance in rats.

An assessment of the behavioral effects of acutely administered anti-cholinesterase compound O-ethyl-N-dimethyl phosphoramidocyanidate (tabun), to male rats was performed in three studies across five dose levels (100-198 micrograms/kg, sc). Doses of 122 micrograms/kg or greater produced conditioned flavor aversions. Spontaneous locomotor activity was significantly decreased at doses of 122 micrograms/kg or greater when compared to vehicle control levels. When administered doses of 168 micrograms/kg or greater, rats exhibited significant decrements in rotarod performance. In addition, the LD50 of tabun was determined to be 240 micrograms/kg. Signs of cholinergic intoxication were not apparent until 144 micrograms/kg tabun or more were given. Behavioral effects were thus obtained at doses that were between 54 and 71% of the LD50.

Animals↗
PubMed1985

Attenuation of cyclophosphamide-induced taste aversions in mice by prochlorperazine, delta 9-tetrahydrocannabinol, nabilone and levonantradol.

A series of experiments were performed with adult CD-1 male mice to evaluate the antiemetic effects of several compounds using the conditioned taste aversion procedure. The antiemetics were administered IP immediately prior to a 30-min conditioning trial in which a novel tasting solution (0.3% saccharin) was presented to the subjects. The emetics, apomorphine and the cancer chemotherapeutic drug cyclophosphamide, were given IP immediately after the conditioning trial at doses that induced taste aversions. Three days later the mice received a two bottle preference test (saccharin vs. water) and the percent saccharin consumed of the total fluid intake was calculated. Doses of the phenothiazine antiemetic prochlorperazine (1 and 3 mg/kg) attenuated the aversions produced by 0.3 and 1.0 mg/kg apomorphine. Doses of drugs currently approved or under clinical investigation as antiemetics in conjunction with cancer chemotherapy, i.e., prochlorperazine (1.0 mg/kg), delta 9-tetrahydrocannabinol (0.3 and 1.0 mg/kg) and nabilone (0.01 and 0.03 mg/kg), significantly attenuated the taste aversions induced by cyclophosphamide. Levonantradol at doses of 0.03 and 0.06 mg/kg, however, did not attenuate cyclophosphamide-induced taste aversions. Conditioned taste aversions produced by emetic drugs warrants investigation as a model for evaluating potential antiemetics.

Animals↗
PubMed1984

Some effects of the formamidine pesticide chlordimeform on the behavior of mice.

Three experiments were performed to determine the behavioral effects of acutely administered chlordimeform (1-56 mg/kg, i.p.) to male mice. In Experiment I, dosages of 30 and 56 mg/kg decreased the amount of time spent investigating a female conspecific. In Experiment II, large dosages of chlordimeform (30 and 56 mg/kg) decreased vertically directed activity (rearing) to a proportionately greater extent than horizontally directed activity (ambulation). In Experiment III, chlordimeform produced conditioned flavor aversions that were intermediate at 10 mg/kg and maximal at 30 mg/kg. In an additional experiment (Experiment IV), the LD50 for chlordimeform was determined to be 95.6 mg/kg. Behavioral effects were thus obtained at dosages that were approximately 10 to 30% of the LD50.

Amidines↗
PubMed1982

A new test for social investigation in mice: effects of d-amphetamine.

A new automated device that concurrently records social investigatory responses and spontaneous motor activity is described and the effects of d-amphetamine are presented. The rectangular Plexiglas apparatus was divided into three compartments, separated from each other by wire mesh screens. A male mouse was placed into the center compartment and the amount of time spent investigating the two adjacent stimulus compartments was recorded using contact circuits. One stimulus compartment housed a female conspecific, while the other remained uninhabited and served as a control for nonsocial investigatory responses. A photo-cell bisected the center compartment and recorded motor activity. Doses of 0, 0.3, 1.0, and 3.0 mg/kg d-amphetamine administered to both sexually naive and sexually experienced male mice resulted in a dose-dependent decrease in investigation of both stimulus chambers, however social investigation was significantly affected at a lower dose. Both groups of males preferred the female to the uninhabited chamber at all but the highest dose of d-amphetamine, which abolished the preference. Locomotor activity for both inexperienced and experienced males increased with increasing doses of d-amphetamine.

Animals↗
PubMed1982

Opiate effects on social investigatory behavior of male mice.

The effects of morphine and naloxone, alone and in combination, on social investigatory behavior and motor activity was examined in CD-1 male mice. Tests were conducted in a Plexiglas apparatus in which a center area was separated from two adjacent stimulus compartments by wire mesh screens. One compartment housed a female conspecific while the other remained empty and served as a control for non-specific investigatory responses. A photocell bisected the center compartment and recorded motor activity. Male mice were placed individually into the center area and the time spent investigating each screen was recorded using contact circuits during the 15-min test. In Experiment 1, males (N = 11) received saline, 0.1, 1.0 and 10.0 mg/kg morphine sulfate IP 20 min prior to testing. The high dose significantly decreased investigation of the female compartment while investigation of the uninhibited chamber and motor activity were not significantly affected. In a second experiment (N = 16), 3, 10 and 30 mg/kg naloxone administered 30 min prior to testing had no significant effect on any of the measures recorded. In a third group of subjects (N = 16), 3 mg/kg naloxone reversed the decrease in female investigation time observed with 10 mg/kg morphine, indicating an opiate mechanism for these results. These data provide further evidence that an animal model can be used to study the disruption of socio-sexual behavior produced by opiates.

Animals↗
PubMed1982

The effects of aggregation on the lethality of phencyclidine in mice.

The lethal effects of d-amphetamine and phencyclidine (PCP) were compared when adult male mice were placed into isolated or aggregated (12 mice/cage) conditions. The LD50 of d-amphetamine decreased approx. 30-fold between isolated (87.9 mg/kg) and aggregated (2.8 mg/kg) conditions. In contrast, PCP showed only a 1.3-fold increase in toxicity between isolated (64.5 mg/kg) and aggregated (48.4 mg/kg) conditions. These results suggest different mechanisms for the acute lethal effects of d-amphetamine and PCP in mice.

Animals↗