Neurotrophic factor expression after CNS viral injury produces enhanced sensitivity to psychostimulants: potential mechanism for addiction vulnerability.
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.
Solbrig
M V
MV
Departments of Neurology, Microbiology, and Molecular Genetics, University of California-Irvine, Irvine, California 92697-4292, USA. msolbrig@uci.edu
Koob
G F
GF
Parsons
L H
LH
Kadota
T
T
Horscroft
N
N
Briese
T
T
Lipkin
W I
WI
D000818:Animals; D015153:Blotting, Western; D001890:Borna Disease / Q000378:metabolism*; D001891:Borna disease virus / Q000472:pathogenicity; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D001923:Brain Chemistry; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure / Q000821:virology; D003913:Dextroamphetamine / Q000494:pharmacology; D004198:Disease Susceptibility / Q000821:virology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009414:Nerve Growth Factors / Q000096:biosynthesis*; D010766:Phosphorylation; D011233:Precipitin Tests; D051381:Rats; D011917:Rats, Inbred Lew; D019966:Substance-Related Disorders / Q000378:metabolism*; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis / Q000378:metabolism
D000697:Central Nervous System Stimulants; D009414:Nerve Growth Factors; D014446:Tyrosine 3-Monooxygenase; D003913:Dextroamphetamine