Clinical and MRI evaluation of psychostimulant neurotoxicity.

The Dopaminergic System is believed to be of central importance to the brain processes involved in the development of human addiction to psychoactive substances (Parsons et al. 1991; Robinson and Berridge 1993). Study of animal models of addiction has revealed that mesocorti-colimbic dopaminergic pathways are necessary for the establishment of repetitive self-administration of psychoactive drugs such as cocaine, opiates, and alcohol (Koob and Bloom 1988). Repetitive self-adminis-tration will not occur following disruption of dopaminergic transmission, including lesions to the nucleus accumbens. This nucleus, anatomically distinct in rats but indistinct from the ventral striatum in man, receives dopaminergic input from presynaptic neurons whose cell bodies reside in the ventral tegmental area (VTA) of the midbrain (Fallon 1988). Cocaine and other psychostimulants bind to the dopaminergic transporter of the presynaptic nerve terminal, thereby blocking reuptake and increasing dopaminergic synaptic transmission (Gawin 1991). This presumably applies to all dopaminergic systems, including mesocorticolimbic projections believed responsible for the repetitive behaviors of addiction as well as the nigrostriatal dopamine system responsible for the coordination of complex movements.