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
✍ Scribed by Michal Izrael; Eddy A. Van der Zee; Theodore A. Slotkin; Joseph Yanai
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 359 KB
- Volume
- 78
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Abstract
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)‐γ and in the basal levels of both PKCγ and PKCβII, the two isoforms known to be relevant to behavioral performance. In contrast, there were no alterations in the response of PKCα, 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 PKCγ 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. © 2004 Wiley‐Liss, Inc.