2000 Articles

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

Solbrig, Marylou V.; Koob, George F.; Parsons, Loren H.; Kadota, Tomoko; Horscroft, Nigel; Briese, Thomas; Lipkin, W. Ian

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 viralinduced 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.