Auditory deficits and motor dysfunction following iminodipropionitrile administration in the rat

The behavioral effects of 3,3'-iminodipropionitrile (IDPN) were studied using reflex modification of the acoustic startle response and figure-eight maze activity. A number of experiments were conducted with separate groups of adult male Long-Evans hooded rats exposed to saline or 50-500 mg/kg IDPN for 3 consecutive days. Auditory thresholds (reflex modification), motor activity, and grip strength were measured 1 day, and 1, 3, and 9 weeks postdosing. Reflex inhibition was monitored daily, prior to, during, and for 7 days following exposure. Auditory thresholds for 5- and 40-kHz tones were elevated approximately 25 dB and 50 dB, respectively. The onset of this auditory dysfunction in the 200-mg/kg/day group, as demonstrated by a loss of reflex inhibition, was 2 days for the 40-kHz tone and 4 days for the 5-kHz tone. Motor activity was increased up to 400% in the 200-mg/kg group, whereas there was no alteration in hindlimb grip strength. These data demonstrate dosage- and time-dependent alterations in auditory and motor function following IDPN exposure.