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Moderate Prenatal Alcohol Exposure and Quantification of Social Behavior in Adult Rats
Published on: December 14, 2014
Prenatal malnutrition alters diazepam-mediated suppression of ultrasonic vocalizations in an age dependent manner
1Center for Behavioral Development & Mental Retardation, M923, Boston University School of Medicine, 715 Albany Street, Boston, MA 02118, USA. jtonkiss@bu.edu
Insights
Prenatal malnutrition in rats alters brain development, leading to increased sensitivity to diazepam (a benzodiazepine) by the second postnatal week. This affects ultrasonic vocalizations and suggests changes in the GABAergic system.
Area of Science:
- Neuroscience
- Developmental Biology
- Pharmacology
Background:
- Prenatal malnutrition can impact neurodevelopment and behavior.
- Benzodiazepines, like diazepam, affect the GABAergic system and can suppress ultrasonic vocalizations (USVs) in pups.
Purpose of the Study:
- To investigate how prenatal malnutrition affects the sensitivity of rat pups to the USV suppressant effects of diazepam.
- To determine if developmental stage influences these effects.
Main Methods:
- Male rat pups from dams fed either a protein-deficient (6% casein) or adequate (25% casein) diet were used.
- Pups were injected with diazepam (0.03–3 mg/kg) or vehicle at postnatal days 7 or 11, followed by cooling stress.
- Ultrasonic vocalizations (USVs) were quantified to measure diazepam's suppressant effect.
Main Results:
- Diazepam dose-dependently suppressed USVs in both groups at both ages.
- No difference in diazepam sensitivity was observed at postnatal day 7.
- At postnatal day 11, prenatally malnourished rats showed significantly greater USV suppression by low doses of diazepam compared to controls.
Conclusions:
- Prenatal malnutrition leads to a differential sensitivity to benzodiazepine receptor agonists in the second postnatal week.
- This altered sensitivity may reflect changes in the developing GABAergic system due to malnutrition.
- The findings suggest adaptive or compensatory changes in the GABAergic system in response to developmental disturbances.
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.
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