[125I]Epibatidine-labelled nicotinic receptors in the extended striatum and cerebral cortex: Lack of association with serotonergic afferents

Amynah A.A. Pradhan, Paul Cumming, Paul B.S. Clarke

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

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.

Original languageEnglish
Pages (from-to)227-236
Number of pages10
JournalBrain Research
Volume954
Issue number2
DOIs
StatePublished - Nov 8 2002

Keywords

  • 5,7-Dihydroxytryptamine
  • Dopamine
  • Nicotinic receptor
  • Nucleus accumbens
  • Serotonin
  • Striatum

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