DEVELOPMENTAL NEUROTOXICITY OF CI-943 - A NOVEL ANTIPSYCHOTIC

Offspring from Sprague-Dawley rats administered 0, 10, 25, or 75 mg/kg /day CI-943 in the diet prior to mating and throughout gestation and l actation (fertility study) or during the last week of gestation and th roughout lactation (perinatal/postnatal study) were evaluated for deve lopmental neurotoxicity using a screen of behavioral tests designed to evaluate rotorod performance, motor activity, acoustic startle respon ding, and learning and memory via a two-way shuttle avoidance paradigm . Treatment-related effects were evident for each behavioral parameter ; they occurred at parentally toxic and nontoxic doses and in the abse nce of detrimental effects on offspring growth and development. Behavi oral effects were in general more robust and occurred at lower doses i n the perinatal-postnatal study than in the fertility study. Vertical movement was the most sensitive motor activity parameter in each study ; decreases of the greatest magnitude occurred during the first minute of testing, and in males more often than in females. Acoustic startle responding and learning and memory were diminished in each study; the se effects were in general concomitant with diminished motor activity, although the pattern of response differed for each study. These resul ts indicate that behavior of offspring from parents administered CI-94 3 was altered regardless of the developmental stage of exposure, altho ugh the pattern of response was dependent on exposure regimen.