Neurotrophic factor expression after CNS viral injury produces enhanced sensitivity to psychostimulants: potential mechanism for addiction vulnerability

J Neurosci. 2000 Nov 1;20(21):RC104. doi: 10.1523/JNEUROSCI.20-21-j0002.2000.

Abstract

Hypothesized risk factors for psychostimulant, amphetamine, and cocaine abuse include dopamine (DA) receptor polymorphisms, HIV infection, schizophrenia, drug-induced paranoias, and movement disorders; however, the molecular, cellular, and biochemical mechanisms that predispose to drug sensitivity or drive the development of addiction are incompletely understood. Using the Borna disease rat, an animal model of viral-induced encephalopathy wherein sensitivity to the locomotor and stereotypic behavioral effects of d-amphetamine and cocaine is enhanced (Solbrig et al., 1994, 1998), we identify a specific neurotrophin expression pattern triggered by striatal viral injury that increases tyrosine hydroxylase activity, an early step in DA synthesis, to produce a phenotype of enhanced amphetamine sensitivity. The reactive neurotrophin pattern provides a molecular framework for understanding how CNS viral injury, as well as other CNS adaptations producing similar growth factor activation profiles, may influence psychostimulant sensitivity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Blotting, Western
  • Borna Disease / metabolism*
  • Borna disease virus / pathogenicity
  • Brain / drug effects
  • Brain / metabolism*
  • Brain / pathology
  • Brain / virology
  • Brain Chemistry
  • Central Nervous System Stimulants / pharmacology
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Corpus Striatum / ultrastructure
  • Corpus Striatum / virology
  • Dextroamphetamine / pharmacology
  • Disease Susceptibility / virology
  • Dose-Response Relationship, Drug
  • Male
  • Motor Activity / drug effects
  • Nerve Growth Factors / biosynthesis*
  • Phosphorylation
  • Precipitin Tests
  • Rats
  • Rats, Inbred Lew
  • Substance-Related Disorders / metabolism*
  • Tyrosine 3-Monooxygenase / analysis
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Central Nervous System Stimulants
  • Nerve Growth Factors
  • Tyrosine 3-Monooxygenase
  • Dextroamphetamine