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Cholinergic synaptic signaling mechanisms underlying behavioral teratogenicity: effects of nicotine, chlorpyrifos, and heroin converge on protein kinase C translocation in the intermedial part of the hyperstriatum ventrale and on imprinting behavior in an avian model.

Publication ,  Journal Article
Izrael, M; Van der Zee, EA; Slotkin, TA; Yanai, J
Published in: J Neurosci Res
November 15, 2004

A wide variety of otherwise unrelated neuroteratogens elicit a common set of behavioral defects centering around cholinergic contributions to cognitive function. We utilized the developing chick to overcome confounds related to maternal effects and compared the actions of nicotine, chlorpyrifos, and heroin on cholinergic signaling in the intermedial part of the hyperstriatum ventrale (IMHV), which controls imprinting behavior. Chicken eggs were injected with nicotine (10 mg/kg of egg), chlorpyrifos (10 mg/kg of egg), or heroin (20 mg/kg of egg; all doses below the threshold for dysmorphology) on incubation days (ID) 0 and 5, and then tests were conducted posthatching. All three compounds elicited significant deficits in imprinting behavior. We also found defects in cholinergic synaptic signaling specifically involving the muscarinic receptor-mediated membrane translocation of protein kinase C (PKC)-gamma and in the basal levels of both PKCgamma and PKCbetaII, the two isoforms known to be relevant to behavioral performance. In contrast, there were no alterations in the response of PKCalpha, an isoform that does not contribute to the behavior, nor were cytosolic levels of any of the isoforms affected. Taken together with similar results obtained in rodents, our findings suggest that disparate neuroteratogens all involve signaling defects centering on the ability of cholinergic receptors to elicit PKCgamma translocation/activation and that this effect is direct, i.e., not mediated by maternal confounds. The chick thus provides a suitable model for the rapid screening of neuroteratogens and elucidation of the mechanisms underlying behavioral anomalies.

Duke Scholars

Published In

J Neurosci Res

DOI

ISSN

0360-4012

Publication Date

November 15, 2004

Volume

78

Issue

4

Start / End Page

499 / 507

Location

United States

Related Subject Headings

  • Time Factors
  • Signal Transduction
  • Protein Kinase C
  • Nicotine
  • Neurology & Neurosurgery
  • Narcotics
  • Motor Activity
  • Models, Animal
  • Imprinting, Psychological
  • Heroin
 

Citation

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Chicago
ICMJE
MLA
NLM
Journal cover image

Published In

J Neurosci Res

DOI

ISSN

0360-4012

Publication Date

November 15, 2004

Volume

78

Issue

4

Start / End Page

499 / 507

Location

United States

Related Subject Headings

  • Time Factors
  • Signal Transduction
  • Protein Kinase C
  • Nicotine
  • Neurology & Neurosurgery
  • Narcotics
  • Motor Activity
  • Models, Animal
  • Imprinting, Psychological
  • Heroin