Motor response of 14-month-old female mice exposed to diazepam prenatally.

Abstract

The response of adult female mice to diazepam (DZ) can be sculpted by the prenatal experience with the drug. Experiments were performed in ICR strain (Harlan México) mice exposed in utero to DZ. They were born from dams injected (s.c.) with 2.7 mg/kg/bw of DZ or just saline solution from day 6 to 17 of pregnancy. They were maintained at 12:12 dark/light cycles with food and water ad libitum. On the experimental day, mice were introduced in an activity meter (actometer) for 5 min. Recordings were run at 25 mm/min. The time they remained motionless or clearly sleepy was determined in millimeters. After that, all animals received (s.c.) 2.7 mg/kg/bw of DZ; 15 min later they were introduced into the actometer again for 5 min. Before DZ, control animals injected with saline during gestation showed 1.57 +/- 0.53 mm and the experimental (DZ) prenatally exposed to DZ, 3.69 +/- 1.72 mm (p =0.27). After DZ, control animals remained motionless for 37.27 +/- 6.77 mm and DZ mice, 59.95 +/- 7.10 mm (p=0.03). This result indicates a significantly larger response to DZ in the pretreated animals, suggesting that exposure of the developing fetus to the drug may lead to persistent (14 months) morphological alterations in several areas of the central nervous system with physiological repercussion on motor behavior and learning, sometimes attributed to brain circuitry modifications or to the developmental vulnerability of synaptic neurochemical mechanisms.