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.
Landauer
M R
MR
Department of Behavioral Sciences, Armed Forces Radiobiology Research Institute, Bethesda, MD 20814-5145.
Davis
H D
HD
Dominitz
J A
JA
Weiss
J F
JF
D004999:Amifostine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects*; D009946:Organothiophosphorus Compounds / Q000494:pharmacology*; D013997:Time Factors
D009946:Organothiophosphorus Compounds; D004999:Amifostine