Altered responsiveness to stress and NMDA following prenatal exposure to cocaine

Pregnant Sprague-Dawley rats were treated once daily with 40-mg/kg cocaine or saline from gestation days (GD) 12 to 21. A third group of pregnant darn s was used as a pairfed control. Male and female offspring were examined fo r stress endurance response as determined by the cold-water swim test on po stnatal days (PND) 21, 30, 40, and 60. Male and female offspring exposed to cocaine in utero were found to have diminished tolerance and altered hormo nal response to stress. Moreover, prenatal cocaine exposure has been associ ated with significant increases in severity ofN-methyl-D-aspartate (NMDA; 3 5 mg/kg) behavioral responses (tail twitches, wetdog shaking, and convulsio n) as compared to control. Examining the experimental groups for pain sensi tivity using the tail-flick and the hot-plate methods indicated that prenat al cocaine exposure altered pain sensitivity. NMDA receptor binding studies showed an increase in receptor density in the hippocampus and hypothalamus of the cocaine-treated group. These results indicate that gestational coca ine exposure is associated with long-term alterations in response to stress , NMDA receptor, and pain sensitivity in the rat offspring. (C) 2001 Elsevi er Science Inc. All rights reserved.