Effects of the neurotoxin 3,3'-iminodipropionitrile on acoustic startle and locomotor activity in rats: a comparison of functional observational and automated startle assessment methods.
Iminodipropionitrile (IDPN) is a neurotoxin that has been used in the validation of the U.S. Environmental Protection Agency's Functional Observational Battery (FOB), including acoustic startle. We compared the FOB clicker startle method to an automated procedure. IDPN was administered IP to male Long-Evans rats in three daily doses of 0, 100, 200, or 400 mg/kg (N = 8 per group). There was a significant effect of IDPN on clicker startle that was attributable to reduced startle in the IDPN-400 group. There were multiple significant effects of IDPN on automated startle. The overall effect of IDPN on automated startle was to reduce startle amplitude in the IDPN-400 and -200 groups. In addition, the IDPN-400 group showed startle reductions on all days, whereas the IDPN-200 group showed reduced startle primarily on day 1. IDPN also significantly altered locomotor activity, which was included as an internal check on IDPN's efficacy. The typical pattern of hypolocomotion was found on day 2 posttreatment in the IDPN-400 and -200 groups, followed by hyperlocomotion on all subsequent days in the IDPN-400 group. The startle results demonstrated that automated startle is more sensitive (at least for IDPN treatment), eliminates observer judgments, and provides interval-scaled data compared to the clicker method. However, automated startle also requires additional initial cost and more testing time per animal when multiple trials are presented.
Fukumura
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M
Division of Developmental Biology, Children's Hospital Research Foundation, OH 45229-3039, USA.
Sethi
N
N
Vorhees
C V
CV
D000818:Animals; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009498:Neurotoxins / Q000633:toxicity*; D009570:Nitriles / Q000633:toxicity*; D051381:Rats; D013216:Reflex, Startle / Q000187:drug effects*; D018675:Toxicity Tests / Q000379:methods*
D009498:Neurotoxins; D009570:Nitriles; C008110:3,3'-iminodipropionitrile