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

John Tonkiss1, Janina Galler

  • 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.

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