dizocilpine-maleate and 3-3--iminodipropionitrile

Developmental neurotoxicity (DNT) testing assesses potentially adverse effects on the developing nervous system. The present DNT study was conducted to generate historical data with the Wistar Han (WH) and Sprague Dawley (SD) rat strains, commonly used in Europe and the US, respectively. Potential differences between these strains in DNT endpoints have not been extensively investigated. Motor activity, startle response, learning and memory testing, and neurological (quantitative and qualitative) examinations were conducted using three groups of control, prenatally exposed (to Methylazoxymethanol [MAM] on gestation Day 15) and acutely treated (with IDPN, MK-801 or Chlorpromazine) animals for each strain. The positive controls produced clear effects in most endpoints investigated, with limited functional differences in baseline behavior and positive control sensitivity. However, SD rats were considerably more susceptible to MAM-induced learning and memory impairments and neurological damage. These data highlight differential sensitivity between the strains, which may require risk assessment consideration for developmental neurotoxicants.

Topics: Animals; Behavior, Animal; Brain; Chlorpromazine; Control Groups; Dizocilpine Maleate; Female; Learning; Male; Memory; Methylazoxymethanol Acetate; Motor Activity; Neurotoxicity Syndromes; Neurotoxins; Nitriles; Pregnancy; Prenatal Exposure Delayed Effects; Rats; Rats, Sprague-Dawley; Rats, Wistar; Reflex, Startle; Species Specificity