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Miniature swine convulsed spontaneously within 30 seconds after a 10,000-rad dose of 30 MeV electrons was delivered to the brain. The seizures ended 2 to 5 minutes later. Since alterations in gamma-aminobutyric acid (GABA) metabolism occur in and may be an underlying cause of a variety of convulsive disorders, regional brain concentrations of GABA and activities of L-glutamic acid decarboxylase (E.C.4.1.1.15) (GAD) were determined in control and irradiated miniature swine. The hypothalamus and midbrain had the highest GABA concentration and GAD activity, followed, in decreasing order of GABA concentration, by the caudate nucleus, thalamus, hippocampus, cerebral cortex and cerebellum. At four minutes after irradiation, GABA concentrations did not change significantly in any brain region examined; the largest apparent change was a decline from 2.31 plus or minus .13 to 2.04 plus or minus .11 micromoles g wet weight in the thalamus. Concurrently, GAD activity in the thalamus increased significantly from 238 plus or minus 7 to 315 plus or minus 29 micromoles/h per g protein. (Modified author abstract)

The metabolism of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) was studied in rats subjected to 10,000 or 20,000 rads of pulsed mixed gamma-neutron radiation. Whole brain GABA levels were found to rise above control levels by 20 minutes following 10,000 rads and as early as one minute following 20,000 rads. L-glutamic acid decarboxylase activity was also observed to rise as early as one minute following either dose of radiation. The results are consistent with the hypothesis that GABA is involved in the etiology of the transient central nervous system disorders (apathy, disorientation, ataxia) observed in rats shortly after high doses of ionizing radiation.

Thirty-two miniature pigs were trained by shock avoidance conditioning to traverse a two-chambered shuttlebox. Eight unshielded pigs (whole-body exposed) received midline tissue doses (MTD) of about 13,000 rads of pulsed, mixed gamma-neutron radiations to the head and trunk. Eight head- shielded and eight trunk-shielded pigs received doses to the unshielded part of the body that were equivalent to the doses received by unshielded animals. Four trunk-shielded pigs received 6000 rads to the head, and four others received 3000 rads to the head. MTD behind the shield (at the middle of the head or trunk) was less than 7 percent of the MTD to the same point without a shield in place. Postirradiation performance was evaluated. All unshielded pigs suffered early transient incapacitation (ETI) or immediate, permanent complete incapacitation (PCI); several early deaths (within 4 hours) occurred among these animals. Head shielding prevented ETI, immediate PCI, and early deaths, but trunk shielding did not. However, trunk-shielded subjects that escaped the early death performed and survived longer than most head-shielded or unshielded pigs. ETI occurred in all of the trunk-shielded pigs that received 6000 rads and in one of four that received 3000 rads; however, early deaths did not occur and survival times were much longer than those previously reported for unshielded pigs that received comparable doses.

Procedures for training pigs by shock avoidance conditioning to perform a shuttlebox and a visual discrimination problem are described. Pigs achieved stable performance levels of better than 95% shock avoidance in six and 35 days for the shuttlebox and discrimination problem, respectively. Such stable and accurate performances are required for assessing behavioral effects of independent variables. (Author)

A procedure in which beagles were trained by shock avoidance conditioning to perform a discrimination task cued by visual and auditory stimuli is described. The time required to train most dogs averaged 50 days. When trained, dogs performed at better than 95 percent correct response. The techniques can be carefully controlled to produce standardized trained animals for applied behavioral research. (Author)

Clinical symptoms and performance were evaluated after shuttlebox-trained miniature pigs received two 4400-rad doses separated by time intervals of .0001 to 30 minutes. The doses were delivered to the head by 45 MeV electrons from the AFRRI electron linear accelerator (LINAC). There was no significant difference in neurological symptoms (convulsions, coma, ataxia) or in performance after the second dose between animals that received the two doses .0001 or 0.3 minute apart. As the time interval between doses was increased from 0.3 to 3 minutes, however, neurological symptoms declined and performance improved markedly after the second dose. When the doses were 30 minutes apart, the pigs showed no decrease in performance within the initial 30 minutes postirradiation. It was concluded that more than physicochemical processes were involved in the increased radioresistance to the second dose of radiation. (Author)

The postirradiation performance of miniature pigs trained to work a shuttlebox problem was compared to that of miniature pigs trained to work a visual discrimination problem. The pigs were whole-body exposed to a gamma ray field produced by the AFRRI-TRIGA reactor operated in the pulse mode (incident neutron to gamma ratio of 0.06) and received midline tissue doses to the brain of 1200 to 3300 rads. The major difference in performance occurred during the first 30 minutes after irradiation. At the doses used in this study, discrimination-trained pigs experienced a more severe and prolonged period of early temporary performance decrement than did the shuttlebox-trained pigs. The ED50 or 50 percentile midbrain dose for early performance decrement was calculated to be 1870 and 2380 rads for the discrimination-trained and shuttlebox-trained pigs, respectively. (Author)

Trained miniature pigs were irradiated in a nuclear reactor-produced gamma ray field. Dose rates at the midline of the brain were 470, 1000, 1500, 2000, or approximately 10,000,000 (pulsed irradiation) rads/minute. Doses ranged from 1500 to 14,700 rads. Postirradiation performance data were used to calculate for each dose rate the most probable dose that would cause 50 percent of the animals to perform unsatisfactorily (ED50). The miniature pigs' response varied markedly with dose rate at less than 2000 rads/minute; ED50's were 10,570, 7780, 2500, and 2380 rads, respectively, for 470, 1000, 1500, 2000, and 10 to the 7th power rads;minute. Survival times, however, did not appear to be dependent upon dose rate. (Author)

An automated assay for determination of glutamic acid decarboxylase activity is described. The PCO2 of an incubation medium is used as a measure of total CO2 formed by enzymic decarboxylation of glutamate. Details of manifold construction, reagent composition, and data concerning the reliability of the method are presented. (Author)

Trained miniature pigs were whole-body irradiated in a nuclear reactor-produced neutron field (incident neutron to gamma ratio of 10). Their postirradiation performance was compared to that of pigs similarly irradiated in a gamma ray field from the same reactor (incident neutron to gamma ratio of 0.06). The dose rate at the midline of the brain was approximately 2000 rads/min for all irradiations; midbrain doses ranged from 1500 to 36,500 rads. Response of the pigs to supralethal doses from the neutron field notably differed from their response to similar doses from the gamma ray field. Early performance decrement, early transient incapacitation, and immediate permanent incapacitation occurred following much lower doses from the gamma ray field than from the neutron field. At doses greater than 11,000 rads, survival times of the neutron-irradiated pigs were on the average much longer than those of the gamma-irradiated pigs. Thus, the gamma rays were markedly more effective than the fission neutrons for producing the severe central nervous system damage manifested by pronounced early performance decrement and death within 48 hours. The relative effectiveness of the neutron field was 0.23 using the reactor-produced gamma ray field as the reference radiation and the 50 percentile midbrain dose (9ED50) for early performance decrement as the biological end point. (Author)

Miniature pigs were trained to traverse, on cue, a two-chambered shuttlebox. Six groups of five to eight pigs received a 4400-rad midline tissue dose of pulsed mixed gamma-neutron radiation followed 1/2, 1, 5, 15, 24, or 51 hours later by a second dose of equivalent magnitude. Two other groups of eight pigs received a lower initial dose (1700 or 3400 rads) followed 1 hour later by a second dose of 4800 to 5000 rads. In addition, unfractionated doses of either 4500 or 8600 rads were given to two groups of six pigs. Regardless of the time interval between the two 4400-rad doses, performance was generally better after the second dose than after the first. Early transient incapacitation, accompanied always by convulsions, and occasionally by coma, consistently occurred after the first dose but was infrequent after the second. When early transient incapacitation did occur after the second dose, it was generally shorter than after the first dose and accompanied by ataxia and disorientation; convulsions and coma were very infrequent. Because of this reduced response to the second 4400-rad dose, performance after an 8800-rad fractionated dose was markedly better than after an 8600-rad unfractionated dose. (Author)

Miniature pigs were trained by shock avoidance conditioning to traverse, on cue, a two-chambered shuttlebox and performance was evaluated after the pigs received mid-line tissue doses of pulsed, mixed gamma-neutron radiations ranging from 1000 to 14,700 rads. At 2400 rads or more, most pigs were incapacitated with severe convulsions almost immediately after irradiation. At doses of 2400 to 5000 rads this incapacitation often lasted less than 5 minutes after which the animals began to recover and perform. At higher doses, most animals were more severely affected. They became comatose and did not begin to recover until 15 to 50 minutes postirradiation. After recovering from early transient incapacitation the pigs worked for a time at relatively normal levels. Later their performance degenerated and the pigs became permanently incapacitated a few hours before death. At doses of 7600 rads and higher, some of the animals recovered only partially from the early transient incapacitation before becoming permanently incapacitated; and at 13,200 rads or more, most animals were permanently incapacitated immediately after irradiation. (Author)

Miniature pigs were trained to traverse on cue a two-chambered shuttlebox. The pigs received either unfractionated (6500, 8600, 11,600, or 13,000 rads) or fractionated (6800, 8500, 11,000, or 13,300 rads) doses of pulsed mixed gamma-neutron radiation. The fractionated doses were delivered as two equal fractions 5 hours apart. Miniature pig performance after the second half of the fractionated dose was similar to or better than the performance observed after the first half of the dose. The pig's performance was markedly better when the dose was fractionated than when it was unfractionated; early transient incapacitation was shorter, and acceptable performance was achieved earlier and lasted longer. Also, mean survival times of the pigs that received fractionated doses were longer. Possible mechanisms which may be responsible for the reduced effectiveness of the fractionated doses are discussed. (Author)

Gamma-aminobutyric acid (GABA) metabolism was studied in rats chronically exposed to 2.86 GHz microwaves at an incident power level of 10 mW/sq cm or acutely exposed to incident power levels of 40 or 80 mW/sq cm. No changes occurred in whole brain GABA levels or L-glutamic decarboxylase activity following these exposures. These results suggest that an altered GABA metabolism is not involved in reported responses of the nervous system to microwave exposure. ( Author)

Nine beagle dogs were trained by shock avoidance conditioning to work a discrimination problem cued by visual and auditory stimuli. The animals received 5200- to 17,600-rad midline tissue doses of pulsed mixed gamma-neutron radiation, and their postirradiation performance was evaluated. During the first 60 minutes after irradiation, random, brief periods of performance decrement frequently occurred. Dogs that received less than 10,000 rads performed at or near preirradiation levels several days until they became permanently incapacitated shortly before death. After doses of 10,000 rads or more most dogs performed satisfactorily for only a few minutes to hours. Their condition then worsened precipitously and the dogs died shortly thereafter. (Author)