Prenatal malnutrition alters diazepam-mediated suppression of ultrasonic vocalizations in an age dependent manner

Abstract

The sensitivity of prenatally malnourished rats to the ultrasonic vocalization (USV) suppressant effect of diazepam (a non-specific benzodiazepine (BZ) receptor agonist) was investigated. Male offspring of dams provided with a protein deficient diet (6% casein) for 5 weeks prior to mating and throughout pregnancy were compared to the offspring of mothers provided with a diet of adequate protein content (25% casein). At postnatal day 7 or 11, pups were injected with vehicle or one of five doses of DZ (0.03, 0.1, 0.3, 1 or 3mg/kg) 30 min after removal from their dam. Thirty minutes later they were subjected to 2 min of cooling on a 20 degrees C surface and their USVs were quantified. DZ dose-dependently suppressed USV at both ages. At P7, the USV suppressant effect of DZ was the same for both groups. However, by P11 the prenatally malnourished rats showed significantly greater suppression of USV by 0.03 and 0.1mg/kg DZ than well-nourished controls. These differences were not related to degree of temperature loss or body weight. Thus, differential sensitivity to BZ receptor agonists develops in the second postnatal week in prenatally malnourished rats. This reflects either an altered program of development of the GABAergic system, or adaptive, compensatory changes in the GABAergic system in response to more extensive functional disturbances in the developing brain.

FIGURE 1

Mean body temperature of prenatally malnourished (6/25, open bars) and well-nourished (25/25, solid bars) rat pups 30 min after removal from the mother and confinement in a warmed cage (Baseline); 30 min after an injection of diazepam at one of five doses (DZ); and, 2 min after additional cooling on a 20°C surface (DZ & Cooling) at (a) Postnatal day 7 (25/25 group, n=10; 6/25 group, n=12 for each DZ dose group), or (b) Postnatal day 11 (25/25 group, n=9; 6/25 group, n=10 for each DZ dose group). Vertical bars represent the SEM. *6/25 significantly less than 25/25, p<0.05 (Tukey)

FIGURE 2

Left panels - Mean number of ultrasonic vocalizations (USV) emitted by prenatally malnourished (6/25, open bars) and well-nourished (25/25, solid bars) pups over a 2 min period of cooling on a 20°C surface 30 min after an injection of vehicle (VEH). Right panels – Mean USV rate following five doses of diazepam (DZ) expressed as a percentage of the vehicle control pup for the same litter (a) Postnatal day 7 (25/25 group, n=10; 6/25 group, n=12 for each DZ dose group), or (b) Postnatal day 11 (25/25 group, n=9; 6/25 group, n=10 for each DZ dose group). Vertical bars represent the SEM. *6/25 significantly less than 25/25, p<0.05 (Tukey).