DOPAMINE TRANSPORTER IMMUNOREACTIVITY IN RAT-BRAIN

The dopamine transporter (DAT) is a primary site for the action of coc aine in inducing euphoria. Its action is necessary for the selectiviti es of dopaminergic neurotoxins that provide the best current experimen tal models of Parkinson's disease. In the present report, rat dopamine transporter-like immunoreactivity (iDAT) was assessed by immunohistoc hemistry using newly developed polyclonal antisera raised against conj ugated peptides corresponding to sequences found in the dopamine trans porter's carboxy- and amino-termini. Dense iDAT was observed in patter ns consistent with neural processes and terminals in the striatum, nuc leus accumbens, olfactory tubercle, nigrostriatal bundle, and lateral habenula. Perikarya in the substantia nigra pars compacta were immunos tained with moderate intensity using one of two immunohistochemical me thods, while scattered ventral tegmental area perikarya were stained w ith somewhat less intensity. Immunoreactive neuronal processes with ax onal and dendritic morphologies were stained in the substantia nigra a nd the paranigral and parabrachialis pigmentosus nuclei of the ventral tegmental area, while sparser processes were noted more medially in t he ventral tegmental area. Neuronal processes were found in several la minae in the cingulate cortex, with notable fiber densities in the sup erficial aspects of lamina I and laminae II/III. The intensities of im munoreactivities in striatum and cerebral cortex were dramatically att enuated ipsilateral to nigrostriatal bundle B-hydroxydopamine lesions. Specificity of immunostaining was supported by agreement of the resul ts using sera directed against two distinct DAT segments, studies with preimmune and preadsorbed sera and studies of the extracted protein. These antisera identify and reveal details of the distribution of DAT immunoreactivity in rat brain and display variations in levels of DAT expression of likely functional significance. (C) 1995 Wiley-Liss, Inc .