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  • Neurotrophic factor expression after CNS viral injury produces enhanced sensitivity to psychostimulants: potential mechanism for addiction vulnerability #MMPMID11050146
  • Solbrig MV; Koob GF; Parsons LH; Kadota T; Horscroft N; Briese T; Lipkin WI
  • J Neurosci 2000[Nov]; 20 (21): RC104 PMID11050146garesp_yesshow ga
  • 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.
  • |Animals[MESH]
  • |Blotting, Western[MESH]
  • |Borna Disease/*metabolism[MESH]
  • |Borna disease virus/pathogenicity[MESH]
  • |Brain Chemistry[MESH]
  • |Brain/drug effects/*metabolism/pathology/virology[MESH]
  • |Central Nervous System Stimulants/pharmacology[MESH]
  • |Corpus Striatum/drug effects/metabolism/ultrastructure/virology[MESH]
  • |Dextroamphetamine/pharmacology[MESH]
  • |Disease Susceptibility/virology[MESH]
  • |Dose-Response Relationship, Drug[MESH]
  • |Male[MESH]
  • |Motor Activity/drug effects[MESH]
  • |Nerve Growth Factors/*biosynthesis[MESH]
  • |Phosphorylation[MESH]
  • |Precipitin Tests[MESH]
  • |Rats[MESH]
  • |Rats, Inbred Lew[MESH]
  • |Substance-Related Disorders/*metabolism[MESH]
  • |Tyrosine 3-Monooxygenase/analysis/metabolism[MESH]

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    RC104 21.20 2000