Prenatal alcohol exposure influences the effects of neuroactive steroids on separation-induced ultrasonic vocalizations in rat pups

Betty Zimmerberg, Brenna McDonald

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Fetal alcohol exposure has been reported to be associated with hyper-responsiveness to stress. Using a maternal separation paradigm, this study examined whether prenatal alcohol exposure affected sensitivity to neurosteroid modulation of stress. We have shown that the neuroactive steroid allopregnanolone reduces ultrasonic vocalizations (USVs) after brief maternal separation in week-old rat pups. Prenatal alcohol exposure, however, resulted in reduced sensitivity to this neurosteroid. In this study's first experiment, the behavioral effects of pregnenolone sulfate, a neurosteroid with reportedly opposite modulatory effects on the GABA(A) receptor, were characterized. Pregnenolone sulfate had a triphasic effect on the production of ultrasonic vocalizations and on open field activity. Blockade of conversion of pregnenolone sulfate to allopregnanolone via the 5α-reductase inhibitor 4-MA also blocked the drug-related reduction in USVs. but not the higher-dose augmentation. The enzyme inhibitor alone had no significant effects on USV production, nor did progesterone. These results suggest that the neuroactive steroid pregnenolone sulfate may play an independent role in the stress response after maternal separation as well as being a precursor for the anxiolytic neurosteroid allopregnanolone. In the second experiment, prenatal alcohol exposure was found to eliminate both the low dose USV-reducing effect and the higher dose USV-increasing effect. These results support previous results demonstrating that prenatal alcohol exposure may cause an altered sensitivity to the neuromodulatory effects of neurosteroids.

Original languageEnglish (US)
Pages (from-to)541-547
Number of pages7
JournalPharmacology Biochemistry and Behavior
Volume55
Issue number4
DOIs
StatePublished - Dec 1996
Externally publishedYes

Fingerprint

Ultrasonics
Rats
Steroids
Neurotransmitter Agents
Alcohols
Pregnanolone
Mothers
Anti-Anxiety Agents
Enzyme Inhibitors
GABA-A Receptors
Progesterone
Oxidoreductases
Experiments
Modulation
pregnenolone sulfate
Pharmaceutical Preparations

Keywords

  • 5-pregnen-3b-ol-20-one
  • alcohol
  • fetal alcohol syndrome
  • maternal separation
  • neuroactive steroids
  • pregnenolone sulfate
  • ultrasonic vocalizations

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

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abstract = "Fetal alcohol exposure has been reported to be associated with hyper-responsiveness to stress. Using a maternal separation paradigm, this study examined whether prenatal alcohol exposure affected sensitivity to neurosteroid modulation of stress. We have shown that the neuroactive steroid allopregnanolone reduces ultrasonic vocalizations (USVs) after brief maternal separation in week-old rat pups. Prenatal alcohol exposure, however, resulted in reduced sensitivity to this neurosteroid. In this study's first experiment, the behavioral effects of pregnenolone sulfate, a neurosteroid with reportedly opposite modulatory effects on the GABA(A) receptor, were characterized. Pregnenolone sulfate had a triphasic effect on the production of ultrasonic vocalizations and on open field activity. Blockade of conversion of pregnenolone sulfate to allopregnanolone via the 5α-reductase inhibitor 4-MA also blocked the drug-related reduction in USVs. but not the higher-dose augmentation. The enzyme inhibitor alone had no significant effects on USV production, nor did progesterone. These results suggest that the neuroactive steroid pregnenolone sulfate may play an independent role in the stress response after maternal separation as well as being a precursor for the anxiolytic neurosteroid allopregnanolone. In the second experiment, prenatal alcohol exposure was found to eliminate both the low dose USV-reducing effect and the higher dose USV-increasing effect. These results support previous results demonstrating that prenatal alcohol exposure may cause an altered sensitivity to the neuromodulatory effects of neurosteroids.",
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