title: Synergistic interaction between serotonin-2 receptor and dopamine D1 receptor stimulation on striatal preprotachykinin mRNA expression in the 6-hydroxydopamine lesioned rat.
abstract: The regulation of striatal preprotachykinin (PPT) mRNA expression can be mediated through both dopamine (DA) D1 and serotonin (5-HT) 5-HT2A/2C receptors. In the present study, we used in situ hybridization to examine possible synergistic interactions between 5-HT2A/2C and D1 receptor-mediated regulation of striatal PPT mRNA levels in the rat depleted of DA with 6-hydroxydopamine. Acute administration of the 5-HT2A/2C receptor agonist DOI (2 mg/kg) significantly increased (+75%) PPT mRNA levels in the dorsal striatum. Acute administration of the D1 receptor agonist SKF-38393 (2 mg/kg) did not significantly alter PPT mRNA levels in the dorsal striatum. However, the co-administration of SKF-38393 and DOI produced a significant increase (+300%) in striatal PPT mRNA expression restricted to the periventricular region of the dorsal-medial striatum. This synergistic interaction was not observed in the remaining aspect of the dorsal striatum where DOI alone increased PPT mRNA expression. These data show that 5-HT2A/2C and D1 receptors can act in a synergistic manner to regulate striatal PPT mRNA in a subregion of the DA-depleted striatum.
authors.affiliation: Cellular and Clinical Neurobiology Program, Department of Psychiatry and Behavioral Neurosciences, Wayne State University, School of Medicine, Detroit, MI 48201, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Gresch
authors.forename: P D
authors.initials: PD
authors.lastname: Walker
mesh_terms: D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D003714:Denervation; D004298:Dopamine / Q000494:pharmacology*; D018491:Dopamine Agonists / Q000494:pharmacology*; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization; D008297:Male; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced; D011498:Protein Precursors / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D015320:Tachykinins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000662:Amphetamines; D018491:Dopamine Agonists; D009419:Nerve Tissue Proteins; D011498:Protein Precursors; D012333:RNA, Messenger; D044402:Receptor, Serotonin, 5-HT2A; D044405:Receptor, Serotonin, 5-HT2C; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D015320:Tachykinins; C044206:preprotachykinin; D012701:Serotonin; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D004298:Dopamine