Measurement of the striatal dopamine transporter density and heterogeneityin type 1 alcoholics using human whole hemisphere autoradiography

Dopaminergic mechanisms are involved in the positive reinforcing and addict ing effects of alcohol. Positron emission tomography (PET) and single photo n emission tomography (SPET) studies have indicated alterations in striatal dopamine transporters (DAT) and in presynaptic dopamine (DA) function in a lcoholics, although also contradictory results have been reported. Normal v ariations in blood flow, metabolism, and receptor densities are apparently important to brain function. Such variations are known to decrease during p athophysiological processes, such as epilepsy, whereas normal receptor dist ributions are broadly heterogenous. We evaluated the densities and heteroge neities of striatal DAT in 8 adult-onset, Cloninger type I alcoholics and 1 0 controls using [I-128]N-(3-iodoprop-2E-enyl)-2 beta -carbomethoxy-3 beta- (4 '- methylphenyl)nortropane ([I-125]PE2I) as a ligand for human postmorte m whole hemisphere autoradiography, which provided high resolution images o f the brain when compared with in vivo PET and SPET, The mean density and h eterogeneity of DAT were markedly lower in the alcoholics. A significant li near correlation existed between DAT density and heterogeneity, as well as between DAT densities in the nucleus accumbens and in the dorsal striatum ( caudate and putamen) in alcoholics, but not consistently in controls. The o bserved low DAT density and heterogeneity in the dorsal striatum suggest th at type 1 alcoholics may have a dysfunctional DA system. These data indicat e that human whole hemisphere autoradiography with the analysis of binding heterogeneity may be a relevant tool to measure pathological processes in t he brain. (C) 2001 Academic Press.