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Title: [125I]Epibatidine-labelled nicotinic receptors in the extended striatum and cerebral cortex: lack of association with serotonergic afferents. Author: Pradhan AA, Cumming P, Clarke PB. Journal: Brain Res; 2002 Nov 08; 954(2):227-36. PubMed ID: 12414106. Abstract: In rat extended striatum, most nicotinic cholinoceptors are likely to be presynaptic. A previous report suggested that DA and 5-HT afferents each account for at least 30% of nicotinic binding sites in the striatum. To explore this question further, rats received unilateral infusions of the neurotoxins 5,7-dihydroxytryptamine, 6-hydroxydopamine or vehicle into the medial forebrain bundle, and were sacrificed 3 weeks later. Denervation was quantified by [125I]RTI-55 autoradiography, using separate assay conditions that revealed DA and 5-HT transporters (i.e. DAT and SERT). Nicotinic cholinoceptors were quantified by [125I]epibatidine autoradiography. Infusion of 6-hydroxydopamine depleted DAT but not SERT labelling in all striatal areas (i.e. caudate-putamen, nucleus accumbens core and shell, olfactory tubercle). The serotonergic neurotoxin 5,7-dihydroxytryptamine depleted SERT and, to a lesser extent, DAT labelling. Both neurotoxins reduced [125I]epibatidine binding in striatal areas. Multiple linear regression analysis showed that these reductions in [125I]epibatidine binding were entirely associated with loss of DAT rather than SERT. The DAT-associated proportion of total [125I]epibatidine binding was 36+/-2% (caudate-putamen), 28+/-3% (accumbens core), 27+/-4% (accumbens shell) and 44+/-5% (olfactory tubercle). Cortical [125I]epibatidine binding was unaltered by 5,7-dihydroxytryptamine lesions that reduced SERT labelling by 46 to 73%. In all brain areas, even small (3.4 to 8.8%) SERT-associated reductions in [125I]epibatidine binding would have been detected as statistically significant. In conclusion, we report the failure to detect nAChRs on 5-HT terminals in extended striatum or cerebral cortex, using a sensitive [125I]epibatidine autoradiographic assay.[Abstract] [Full Text] [Related] [New Search]