The rewarding/reinforcing effects of cocaine are produced by blocking reuptake of dopamine by the dopamine transporter (DAT). The DAT gene is expressed in dopaminergic neurons of the ventral midbrain, and serves as the only currently-available marker expressed almost exclusively by these cells. During this FY, we have completed isolation of the complete human DAT gene, and identified frequencies and patterns of linkage disequilibrium between allelic sequence variants in the second, sixth, and ninth exons. Identification of homologous muring genomic sequences from 129 strains has allowed construction of homologous recombinant DAT knockout mice for neurobiologic studies. Work to confirm or extend initial associations of DAT gene markers with attention deficit hyperactivity disorder and with the paranoia that can accompany cocaine abuse continued as more subjects were characterized, while failure of markers at the DAT or synaptic vesicular monoamine transporter (VMAT2) locus to cosegregate with schizophremnia in several pedigrees was reported.
- National Institute on Drug Abuse
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