Dopamine receptor agonists regulate levels of the serotonin 5-HT2A receptor and its mRNA in a subpopulation of rat striatal neurons.
The effects of dopamine receptor agonists on the levels of the striatal serotonin 5-HT2A receptor and its mRNA were investigated in rats lesioned with 6-OHDA as neonates. The mRNA encoding for the 5-HT2A receptor was detected by in situ hybridization histochemistry and the binding of 5-HT2A receptors was revealed with [125I](2,5-dimethoxy-4-iodophenyl)2-aminopropane ([125I]DOI). In adult control unlesioned rats, labeling with the 5-HT2A cRNA probe and with [125I]DOI was concentrated in medial sectors of the striatum. In 6-OHDA-lesioned rats, labeling with the 5-HT2A cRNA probe or with [125I]DOI was increased in the striatum, particularly in its lateral subdivisions. These increases were abolished after chronic systemic administration of the dopamine receptor agonists apomorphine or SKF-38393. The mRNA levels encoding for the 5-HT2A receptor were further measured in individual striatal neurons after double-labeling of sections with a 5-HT2A and a preproenkephalin (PPE) cRNA probe. In control unlesioned rats, 5-HT2A mRNA labeling was distributed in PPE-labeled as well as in PPE-unlabeled striatal neurons. In 6-OHDA-lesioned rats, increased 5-HT2A mRNA labeling was found only in PPE-unlabeled neurons and it was abolished after apomorphine or SKF-38393 administration. These results demonstrate that agonists of dopamine receptors inhibit the expression of 5-HT2A receptors in a subpopulation of presumed striato-nigral neurons. We propose that this regulation plays an important role in the control of motor activity by dopamine and 5-HT in the basal ganglia.
Laprade
N
N
Département d'Anatomie, Faculté de Médecine, Université Laval, Québec, Canada.
Radja
F
F
Reader
T A
TA
Soghomonian
J J
JJ
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D018663:Adrenergic Agents / Q000494:pharmacology; D000662:Amphetamines / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001058:Apomorphine / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive / Q000502:physiology; D018491:Dopamine Agonists / Q000494:pharmacology; D004745:Enkephalins / Q000235:genetics; D005260:Female; D017403:In Situ Hybridization; D007457:Iodine Radioisotopes / Q000378:metabolism; D008845:Microinjections; D009043:Motor Activity / Q000502:physiology; D017072:Neostriatum / Q000166:cytology*; D009474:Neurons / Q000737:chemistry / Q000502:physiology; D016627:Oxidopamine / Q000494:pharmacology; D011247:Pregnancy; D011498:Protein Precursors / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology
D018663:Adrenergic Agents; D000662:Amphetamines; D018491:Dopamine Agonists; D004745:Enkephalins; D007457:Iodine Radioisotopes; D011498:Protein Precursors; D012333:RNA, Messenger; D017447:Receptors, Dopamine D1; D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D016627:Oxidopamine; C033660:preproenkephalin; D001058:Apomorphine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine