Assessment of acute behavioral toxicity of low doses of diisopropylfluorophosphate (DFP) in rats.
The effect on behavior of single subtoxic doses (100 and 600 micrograms/kg i.p., i.e. 1/77 and 1/13 of LD50, respectively) of an organophosphorous compound, diisopropylfluorophosphate (DFP), was studied in male Wistar rats. In the open-field test, the lower dose of DFP tended to increase ambulation, while the higher dose showed a trend towards a decrease in ambulation, rearing and frequency of defecation. In the elevated plus-maze, rotarod, elevated bridges and hot plate tests, DFP-treated rats did not differ significantly from the olive oil-treated controls. DFP significantly impaired the performance of rats in the one-trial passive avoidance task and dose-dependently decreased spontaneous locomotor activity for 4 hours after administration. At the doses used DFP only slightly inhibited acetylcholinesterase activity in the blood and different brain areas. The results show that the higher dose of DFP had an inactivating effect on the behavior of rats, while the lower dose did not markedly change their behavioral pattern. Our findings indicate that anticholinesterase compounds, such as DFP, can alter behavior even after single small subtoxic doses.
Nieminen
S A
SA
Neuroscience Center, University of Kuopio, Finland.
Sirkka
U
U
Lecklin
A
A
Heikkinen
O
O
Ylitalo
P
P
D000110:Acetylcholinesterase / Q000097:blood / Q000378:metabolism; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D007531:Isoflurophate / Q000633:toxicity*; D007928:Lethal Dose 50; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D007531:Isoflurophate; D000110:Acetylcholinesterase