Design and evaluation of an olfactometer for the assessment of 3-methylindole-induced hyposmia.
Few studies objectively evaluate olfactory function in animals following exposure to chemicals that induce nasal toxicity. An olfactometer capable of generating a reproducible olfactory stimulus and measuring an odorant-cued behavioral response was developed for rats from a commercially available two-way shuttle box. The box was modified to deliver the test odorant, acetaldehyde, to either of two chambers separated by a physical barrier consisting of a downward-directed airwall sandwiched between two exhaust panels. Male Fisher 344 rats were trained with either a coupled odorant- or tone-cued active avoidance paradigm in order to compare auditory-cued versus olfactory-cued learning and memory. Odorant-cued animals had faster acquisition and longer retention of the avoidance behavior than tone-cued animals. Animals given the model olfactory toxicant 3-methylindole (3-MI, 400 mg/kg, ip) had reduced odorant-cued avoidance, while no effect on tone-cued behavior was observed. In a follow-up study, additional odorant-trained rats were dosed with 0, 100, 200, or 300 mg/kg of 3-MI ip and olfactory function reassessed 6 days later. Histopathologic evidence of moderate to severe olfactory epithelial damage was observed in all rats 7 days after 3-MI administration. Only the highest 3-MI dose (300 mg/kg) was associated with a significant reduction in odor-cued avoidance behavior as compared to that seen in control. These results indicate that use of this olfactometer can provide a functional assessment of chemically induced olfactory toxicity and complements more routine nasal pathology.
Owens
J G
JG
Chemical Industry Institute of Toxicology, 6 Davis Drive, Research Triangle Park, North Carolina, 27709-2137, USA.
James
R A
RA
Moss
O R
OR
Morgan
K T
KT
Bowman
J R
JR
Struve
M F
MF
Dorman
D C
DC
D000818:Animals; D001273:Atmosphere Exposure Chambers; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D004867:Equipment Design; D008297:Male; D009666:Nose / Q000473:pathology; D009812:Odorants; D000857:Olfaction Disorders / Q000139:chemically induced* / Q000175:diagnosis* / Q000503:physiopathology; D011597:Psychomotor Performance / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D012862:Skatole; D012903:Smell / Q000187:drug effects / Q000502:physiology; D018675:Toxicity Tests
D012862:Skatole