Skip to main content
Journal cover image

Nicotine therapy in adulthood reverses the synaptic and behavioral deficits elicited by prenatal exposure to phenobarbital.

Publication ,  Journal Article
Beer, A; Slotkin, TA; Seidler, FJ; Aldridge, JE; Yanai, J
Published in: Neuropsychopharmacology
January 2005

A major objective in identifying the mechanisms underlying neurobehavioral teratogenicity is the possibility of designing therapies that reverse or offset drug- or toxicant-induced neural damage. In our previous studies, we identified deficits in hippocampal muscarinic cholinergic receptor-induced membrane translocation of protein kinase C (PKC)gamma as the likely mechanism responsible for adverse behavioral effects of prenatal phenobarbital exposure. We therefore explored whether behavioral and synaptic defects could be reversed in adulthood by nicotine administration. Pregnant mice were given milled food containing phenobarbital to achieve a daily dose of 0.5-0.6 g/kg from gestational days 9-18. In adulthood, offspring showed deficits in the Morris maze, a behavior dependent on the integrity of septohippocampal cholinergic synaptic function, along with the loss of the PKCgamma response. Phenobarbital-exposed and control mice then received nicotine (10 mg/kg/day) for 14 days via osmotic minipumps. Nicotine reversed the behavioral deficits and restored the normal response of hippocampal PKCgamma to cholinergic receptor stimulation. The effects were regionally specific, as PKCgamma in the cerebellum was unaffected by either phenobarbital or nicotine; furthermore, in the hippocampus, PKC isoforms unrelated to the behavioral deficits showed no changes. Nicotine administration thus offers a potential therapy for reversing neurobehavioral deficits originating in septohippocampal cholinergic defects elicited by prenatal drug or toxicant exposures.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Neuropsychopharmacology

DOI

ISSN

0893-133X

Publication Date

January 2005

Volume

30

Issue

1

Start / End Page

156 / 165

Location

England

Related Subject Headings

  • Synapses
  • Swimming
  • Signal Transduction
  • Receptors, Nicotinic
  • Psychiatry
  • Protein Kinase C
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Phenobarbital
  • Parasympathetic Nervous System
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Beer, A., Slotkin, T. A., Seidler, F. J., Aldridge, J. E., & Yanai, J. (2005). Nicotine therapy in adulthood reverses the synaptic and behavioral deficits elicited by prenatal exposure to phenobarbital. Neuropsychopharmacology, 30(1), 156–165. https://doi.org/10.1038/sj.npp.1300582
Beer, Avital, Theodore A. Slotkin, Frederic J. Seidler, Justin E. Aldridge, and Joseph Yanai. “Nicotine therapy in adulthood reverses the synaptic and behavioral deficits elicited by prenatal exposure to phenobarbital.Neuropsychopharmacology 30, no. 1 (January 2005): 156–65. https://doi.org/10.1038/sj.npp.1300582.
Beer A, Slotkin TA, Seidler FJ, Aldridge JE, Yanai J. Nicotine therapy in adulthood reverses the synaptic and behavioral deficits elicited by prenatal exposure to phenobarbital. Neuropsychopharmacology. 2005 Jan;30(1):156–65.
Beer, Avital, et al. “Nicotine therapy in adulthood reverses the synaptic and behavioral deficits elicited by prenatal exposure to phenobarbital.Neuropsychopharmacology, vol. 30, no. 1, Jan. 2005, pp. 156–65. Pubmed, doi:10.1038/sj.npp.1300582.
Beer A, Slotkin TA, Seidler FJ, Aldridge JE, Yanai J. Nicotine therapy in adulthood reverses the synaptic and behavioral deficits elicited by prenatal exposure to phenobarbital. Neuropsychopharmacology. 2005 Jan;30(1):156–165.
Journal cover image

Published In

Neuropsychopharmacology

DOI

ISSN

0893-133X

Publication Date

January 2005

Volume

30

Issue

1

Start / End Page

156 / 165

Location

England

Related Subject Headings

  • Synapses
  • Swimming
  • Signal Transduction
  • Receptors, Nicotinic
  • Psychiatry
  • Protein Kinase C
  • Prenatal Exposure Delayed Effects
  • Pregnancy
  • Phenobarbital
  • Parasympathetic Nervous System