Neurotrophic Factor Expression After CNS Viral Injury Produces Enhanced Sensitivity to Psychostimulants: Potential Mechanism for Addiction Vulnerability

• Published in: The Journal of neuroscience Vol. 20; no. 21; pp. 104 - RC104
• Main Authors: Solbrig, Marylou V, Koob, George F, Parsons, Loren H, Kadota, Tomoko, Horscroft, Nigel, Briese, Thomas, Lipkin, W. Ian
• Format: Journal Article
• Language: English
• Published: United States Soc Neuroscience 01.11.2000; Society for Neuroscience
• Subjects: Animals; Blotting, Western; Borna Disease - metabolism; Borna disease virus; 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; Rapid Communication; Rats; Rats, Inbred Lew; Substance-Related Disorders - metabolism; Tyrosine 3-Monooxygenase - analysis; Tyrosine 3-Monooxygenase - metabolism
• ISSN: 0270-6474; 1529-2401
• DOI: 10.1523/jneurosci.20-21-j0002.2000

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.