Effects of ethiofos (WR-2721) and radiation on monkey visual discrimination performance.

WR-2721 (ethiofos) is a promising protector against radiation-induced lethality and may be useful in cancer radiotherapy (Davidson et al . , 1980). However, ethiofos also produces nausea, vomiting, diarrhea, and hypotension, which implies severe behavioral consequences (Bogo et al . , 1985). We studied the effects of ethiofos on behavior in monkeys and its ability to mitigate early transient incapacitation (ETI). ETI is the abrupt cessation of performance (for at least 1 ~min) following rapidly delivered, high doses of radiation and usually occurs 5 10 min after irradiation and lasts for 1 -15 min (Bogo, 1988a). Male rhesus (Macaca mulatta) monkeys (N = 24) were obtained from the Joint Services Primate Breeding Colony, Naval Aerospace Medical Research Laboratory, Pensacola, Florida, and quarantined 60 d for evaluation, tuberculosis testing, and stabilization. Monkeys were maintained in conventional stainless steel, wall-mounted cages in rooms maintained at 72 ± 2°F, with 50% ± 10% relative humidity using 100% conditioned fresh air at 12 air changes per hr. They were provided commercial monkey chow and hyperchlorinated tap water ad libitum, and were kept on a 12 hr light/12 hr dark, full-spectrum light cycle with no twilight. Monkeys seated in plastic chairs were exposed to a TRIGA reactor pulse (50 msec) of neutron/gamma radiation (ratio 0.4). The doses were 14, 16, 22, and 24 Gy. A 22 Gy pulse was used in the ethiofos/radiation condition because it was known to be 90% effective in producing ETI in monkeys performing the speed stress visual discrimination task (SSVDT) (Bogo et al . , 1987). Since the ETI dose was well above the LD 50/30 of 6 Gy for a monkey, ethiofos was not expected to offer any protection from lethality. Ethiofos was given i.v. (saphenous vein) at least 30 min before irradiation. The 200 mg/kg dose was diluted in 60 cc saline and injected with an infusion pump over 5 min. Performance was assessed with either a visual discrimination task (VDT) or an SSVDT. In these shock avoidance tasks, trained monkeys discriminated between a circle and a square (always the correct choice) randomly presented every 10 s on bacldit press-plates. Maximum response time in the VDT was 5.0 s, and 0.7 s or less in the SSVDT. Performance was assessed 15 min before and after ethiofos, during radiation exposure, and for 90 min after irradiation. The test measures were (a) ETI 90 min following radiation, (b) percent correct choice following ethiofos and/or radiation, (c) emesis after ethiofos and/or radiation, and (d) time to death. In the repeat-measure study, the same six monkeys (mean weight 8.3 kg) were tested on the SSVDT as follows: (a) sham ethiofos (saline)/sham radiation (baseline control), (b) ethiofos/sham radiation, and (c) ethiofos/radiation. A three week interval was allowed between tests. At the time of the study the number of large, trained monkeys was limited, and no concurrent radiationonly control group existed to illustrate ETI. Radiation-only controls were obtained from the Armed Forces Radiobiology Research Institute's Primate Behavioral Data Base in smaller but similarly handled monkeys (weight 3.7 kg) (Franz et al . , 1981). The 14 and 16 Gy irradiated monkeys performed the SSVDT, and the 24 Gy irradiated monkeys performed the VDT. All monkeys were monitored before and after exposure to record incidence of emesis and were