Selective correlation of nAChRs and DAT

Abstract

Nicotine has been shown to regulate the dopamine transporter (DAT) in a tissue dependent manner and to affect increase both the function of DAT as well as its surface expression (Middleton et al., 2004; Zhu et al., 2009). Here we have looked for a correlation in DAT distribution with sites rich in nAChRS. The binding of DAT was determined using [125I]RTI‐121 and was compared to that of [125I]EB and [125I]α‐BTX in rat brain using receptor autoradiography. Our preliminary results showed a high level of correlation between DAT to non‐α7 nAChRs primarily in mesolimbic and mesocortical areas, but not so in nigrostriatal areas. In the mesocortical and mesolimbic pathways, there were relatively high levels of non‐α7 nAChRs in habenula, nucleus accumbens, prefrontal cortex and cingulated cortex, but only low levels in the olfactory tubercle, hippocampus or in the VTA. There was little or no correlation between DAT and α7 nAChRs. Only modest levels of α7 nAChRs were found in the hippocampus, mammilary bodies, superior colliculus, lateral hypothalamus and entorhinal cortex, and non where found in substantia nigra, VTA, lateral caudate, or olfactory tubercle, areas rich in DAT. Since new studies have found that increase dopamine release is involved with changes in the level of clearance of DA it is important that we further characterize the nAChRs subtype involved in this regulation. The fact that α7‐containing receptors do not correlate to the distribution of DAT will help narrow future studies to the high affinity receptors.This research was supported by NIH R24 MH067627‐01A to MDG Project 2.