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Ischemia contributes to adverse effects of cocaine on brain development: suppression of ornithine decarboxylase activity in neonatal rat.

Publication ,  Journal Article
Koegler, SM; Seidler, FJ; Spencer, JR; Slotkin, TA
Published in: Brain Res Bull
December 1991

Exposure to cocaine during development has been shown to cause structural and functional alterations in the nervous system. In the current study, the mechanisms underlying these effects were examined in neonatal rats through measurement of ornithine decarboxylase activity, a key regulatory enzyme in the control of neural cell differentiation. Animals were given cocaine (30 mg/kg SC) and ornithine decarboxylase measured 1 and 4 h later in midbrain + brainstem, cerebral cortex and cerebellum. Cocaine caused inhibition of ornithine decarboxylase activity that was not secondary to local anesthesia, as lidocaine was ineffective. The effect of cocaine was independent of direct central actions, as introduction of the drug into the central compartment via intracisternal injection failed to inhibit ornithine decarboxylase. In contrast, prevention of cocaine-induced ischemia by peripheral alpha-adrenergic blockade (phenoxybenzamine) reversed the ornithine decarboxylase inhibition caused by cocaine, and actually unmasked potential stimulatory actions. These data indicate that cocaine-induced ischemia is a major contributor to the net effect of the drug on central nervous system cellular development.

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Published In

Brain Res Bull

DOI

ISSN

0361-9230

Publication Date

December 1991

Volume

27

Issue

6

Start / End Page

829 / 834

Location

United States

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • Ornithine Decarboxylase
  • Neurology & Neurosurgery
  • Lidocaine
  • Injections, Subcutaneous
  • Injections, Intraventricular
  • Cocaine
  • Brain Ischemia
  • Brain
 

Citation

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Koegler, S. M., Seidler, F. J., Spencer, J. R., & Slotkin, T. A. (1991). Ischemia contributes to adverse effects of cocaine on brain development: suppression of ornithine decarboxylase activity in neonatal rat. Brain Res Bull, 27(6), 829–834. https://doi.org/10.1016/0361-9230(91)90217-8
Koegler, S. M., F. J. Seidler, J. R. Spencer, and T. A. Slotkin. “Ischemia contributes to adverse effects of cocaine on brain development: suppression of ornithine decarboxylase activity in neonatal rat.Brain Res Bull 27, no. 6 (December 1991): 829–34. https://doi.org/10.1016/0361-9230(91)90217-8.
Koegler, S. M., et al. “Ischemia contributes to adverse effects of cocaine on brain development: suppression of ornithine decarboxylase activity in neonatal rat.Brain Res Bull, vol. 27, no. 6, Dec. 1991, pp. 829–34. Pubmed, doi:10.1016/0361-9230(91)90217-8.
Journal cover image

Published In

Brain Res Bull

DOI

ISSN

0361-9230

Publication Date

December 1991

Volume

27

Issue

6

Start / End Page

829 / 834

Location

United States

Related Subject Headings

  • Rats, Inbred Strains
  • Rats
  • Ornithine Decarboxylase
  • Neurology & Neurosurgery
  • Lidocaine
  • Injections, Subcutaneous
  • Injections, Intraventricular
  • Cocaine
  • Brain Ischemia
  • Brain