[125I]Epibatidine-labelled nicotinic receptors in the extended striatum and cerebral cortex: lack of association with serotonergic afferents.
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.
Pradhan
Amynah A A
AA
Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir William Osler, Montreal, Quebec, Canada H3G 1Y6.
Cumming
Paul
P
Clarke
Paul B S
PB
D015116:5,7-Dihydroxytryptamine / Q000633:toxicity; D000344:Afferent Pathways / Q000187:drug effects / Q000293:injuries; D000818:Animals; D001345:Autoradiography; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins / Q000032:analysis; D002540:Cerebral Cortex / Q000737:chemistry*; D003042:Cocaine / Q000031:analogs & derivatives* / Q000032:analysis; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000293:injuries; D008562:Membrane Glycoproteins / Q000032:analysis; D026901:Membrane Transport Proteins / Q000032:analysis; D017072:Neostriatum / Q000737:chemistry*; D009419:Nerve Tissue Proteins; D009498:Neurotoxins / Q000633:toxicity; D018722:Nicotinic Agonists; D009714:Nucleus Accumbens / Q000737:chemistry; D009833:Olfactory Pathways / Q000737:chemistry; D016627:Oxidopamine / Q000633:toxicity; D011725:Pyridines; D019275:Radiopharmaceuticals; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000032:analysis*; D012701:Serotonin / Q000378:metabolism; D018490:Serotonin Agents / Q000633:toxicity; D050486:Serotonin Plasma Membrane Transport Proteins
D019086:Bridged Bicyclo Compounds, Heterocyclic; D002352:Carrier Proteins; D050483:Dopamine Plasma Membrane Transport Proteins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009498:Neurotoxins; D018722:Nicotinic Agonists; D011725:Pyridines; D019275:Radiopharmaceuticals; D011978:Receptors, Nicotinic; D018490:Serotonin Agents; D050486:Serotonin Plasma Membrane Transport Proteins; C493216:Slc6a3 protein, rat; C493232:Slc6a4 protein, rat; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; C069723:2beta-carbomethoxy-3beta-(4-iodophenyl)tropane; D016627:Oxidopamine; D003042:Cocaine; C082748:epibatidine; D004298:Dopamine