title: Differential effects of serotonin (5-HT) lesions and synthesis blockade on neuropeptide-Y immunoreactivity and 5-HT1A, 5-HT1B/1D and 5-HT2A/2C receptor binding sites in the rat cerebral cortex.
abstract: The present study was aimed at comparing the effects of serotonin (5-HT) synthesis blockade using chronic administration of p-chlorophenylalanine (PCPA) and 5,7-dihydroxytryptamine injections of variable volume (3 vs. 6 microl) on the density of NPY immunoreactive (Ir) neurons and binding of [3H]8-OH-DPAT, S-CM-G[125I]TNH2 and [125I]DOI to 5-HT1A, 5-HT1B/1D, and 5-HT2A/2C receptors in rat cortical regions. Three weeks after large but partial (89% depletion in 5-HT tissue concentration) lesions of 5-HT neurons no changes in neither NPY immunoreactivity nor 5-HT receptor binding were detected. The complete 5,7-DHT lesions produced increases in the number of NPY-Ir neurons in the upper regions of the cingular (134%), frontal (140%) and parietal cortex (48%) and corresponding decreases in 5-HT2A/2C binding (16-26%). No changes in 5-HT1A and 5-HT1B/1D binding were observed after lesions of this kind. After PCPA treatment, decreases in NPY-Ir neurons density (22-40%) and increases in 5-HT1A and 5-HT1B/1D receptor binding sites (20-50%) were distributed in both upper and deeper cortical regions. The lack of effect of the partial lesion suggests that spared 5-HT neurons may exert compensatory mechanisms up to a large extent. The changes in NPY immunoreactivity and 5-HT2A/2C binding detected in the upper regions of the cortex after complete 5-HT lesions probably result from local cellular rearrangements, whereas blocking 5-HT synthesis has more widespread influence on NPY neurons and on 5-HT1A and 5-HT1B/1D receptor subtypes. Moreover, decreases in DOPAC concentrations detected only after complete lesions suggest that the involvement of catecholaminergic transmission may also differentiate 5,7-DHT and PCPA treatments. Altogether, these data suggest that different receptor subtypes might be involved in 5-HT-NPY relationships.
authors.affiliation: CNRS UPR 9013 - Laboratoire de Neurobiologie Cellulaire et Fonctionnelle, Marseille, France.
authors.forename: V
authors.initials: V
authors.lastname: Compan
authors.forename: L
authors.initials: L
authors.lastname: Segu
authors.forename: M C
authors.initials: MC
authors.lastname: Buhot
authors.forename: A
authors.initials: A
authors.lastname: Daszuta
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D015116:5,7-Dihydroxytryptamine / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002540:Cerebral Cortex / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism*; D004151:Dipeptides / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D005260:Female; D010134:Fenclonine / Q000494:pharmacology; D007457:Iodine Radioisotopes; D009473:Neuronal Plasticity / Q000502:physiology; D009478:Neuropeptide Y / Q000032:analysis* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D044346:Receptor, Serotonin, 5-HT1D; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000032:analysis* / Q000276:immunology; D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin / Q000031:analogs & derivatives / Q000096:biosynthesis* / Q000494:pharmacology; D018490:Serotonin Agents / Q000494:pharmacology; D014316:Tritium
chemical_list: D000662:Amphetamines; D004151:Dipeptides; D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D044346:Receptor, Serotonin, 5-HT1D; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D018490:Serotonin Agents; D014316:Tritium; D015102:3,4-Dihydroxyphenylacetic Acid; C072128:serotonin-O-carboxymethyl-Gly-Tyr; D015116:5,7-Dihydroxytryptamine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D010134:Fenclonine; D004298:Dopamine