Serotonin 2A receptor regulation of striatal neuropeptide gene expression is selective for tachykinin, but not enkephalin neurons following dopamine depletion.
Serotonin (5-HT) 2A receptor-mediated regulation of striatal preprotachykinin (PPT) and preproenkephalin (PPE) mRNAs was studied in adult rodents that had been subjected to near-total dopamine (DA) depletion as neonates. Two months following bilateral 6-hydroxydopamine (6-OHDA) lesion, PPT mRNA levels decreased 59-73% across dorsal subregions of the rostral and caudal striatum while PPE transcripts increased 61-94%. Four hours after a single injection of the serotonin 2A/2C receptor agonist, (+/-)-1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane (DOI; 1 mg/kg), PPT mRNA expression was significantly increased in DA-depleted rats across all dorsal subregions of the rostral and caudal striatum as compared to 6-OHDA-treated animals alone. In the intact rat, DOI did not influence PPT mRNA levels in the rostral striatum, but did raise expression in the caudal striatum where 5-HT2A receptors are prominent. DOI did not regulate PPE mRNA levels in any striatal sub-region of the intact or DA-depleted rat. Prior administration of the 5-HT2A/2C receptor antagonist, ritanserin (1 mg/kg) or the 5-HT2A receptor antagonist, ketanserin (1 mg/kg) completely blocked the DOI-induced increases in striatal PPT mRNA in both lesioned and intact animals. The ability of ketanserin to produce identical results as ritanserin suggests that 5-HT2A receptor-mediated regulation is selectively strengthened within tachykinin neurons of the rostral striatum which are suppressed by DA depletion. The selectivity suggests that 5-HT2A receptor upregulation following DA depletion is capable of regulating tachykinin biosynthesis without influencing enkephalin expression in striatal output neurons.
Basura
G J
GJ
Department of Anatomy and Cell Biology, Wayne State University School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.
Walker
P D
PD
D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis; D000662:Amphetamines / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis / Q000172:deficiency* / Q000502:physiology; D004745:Enkephalins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology*; D006897:Hydroxyindoleacetic Acid / Q000032:analysis; D017403:In Situ Hybridization; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000145:classification / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin / Q000502:physiology*; D016713:Ritanserin / Q000494:pharmacology; D012701:Serotonin / Q000032:analysis / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013565:Sympatholytics / Q000633:toxicity; D015320:Tachykinins / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic
D000662:Amphetamines; D004745:Enkephalins; D011498:Protein Precursors; D044402:Receptor, Serotonin, 5-HT2A; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D013565:Sympatholytics; D015320:Tachykinins; C044206:preprotachykinin; D015102:3,4-Dihydroxyphenylacetic Acid; D016713:Ritanserin; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D016627:Oxidopamine; C033660:preproenkephalin; D007650:Ketanserin; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine