[I]Epibatidine-labelled nicotinic receptors in the extended striatum and cerebral cortex: lack of association with serotonergic afferents |
| |
Authors: | Amynah AA Pradhan Paul Cumming Paul BS Clarke |
| |
Institution: | a Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6;b PET Center, Århus General Hospital, Århus, Denmark DK-8000 |
| |
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. |
| |
Keywords: | Nicotinic receptor Dopamine Serotonin Striatum Nucleus accumbens 5 7-Dihydroxytryptamine |
本文献已被 ScienceDirect 等数据库收录! |
|