Heroin neuroteratogenicity: delayed-onset deficits in catecholaminergic synaptic activity.

Published

Journal Article

Prenatal heroin exposure evokes neurochemical and behavioral deficits that, in part, reflect disruption of septohippocampal cholinergic function. In earlier studies, we found that cholinergic synaptic defects involve primary changes in cell signaling proteins that are shared by other transmitter systems. In the current study, we determined whether heroin also targets noradrenergic and dopaminergic inputs that operate through the same signaling cascades. Mice exposed to prenatal heroin showed significant deficits in norepinephrine and dopamine levels and much more pronounced effects on neurotransmitter turnover, an index of synaptic activity. Adverse effects were not present in the immediate postnatal period but rather emerged just before weaning and worsened subsequently. By young adulthood, the most highly-affected regions (hippocampus, cerebral cortex) displayed almost complete inactivation of noradrenergic and dopaminergic tonic activity. These effects arise after prior deficits in cell signaling are discernible, suggesting that the presynaptic effects are secondary to actions on signal transduction cascades shared by numerous neurotransmitter inputs and targeted by other neuroteratogens. These results may explain why apparently unrelated developmental neurotoxicants may ultimately produce a common set of neurochemical and behavioral anomalies.

Full Text

Duke Authors

Cited Authors

  • Slotkin, TA; Seidler, FJ; Yanai, J

Published Date

  • September 12, 2003

Published In

Volume / Issue

  • 984 / 1-2

Start / End Page

  • 189 - 197

PubMed ID

  • 12932853

Pubmed Central ID

  • 12932853

International Standard Serial Number (ISSN)

  • 0006-8993

Digital Object Identifier (DOI)

  • 10.1016/s0006-8993(03)03152-4

Language

  • eng

Conference Location

  • Netherlands