DOPAMINE-RECEPTOR AGONISTS REGULATE LEVELS OF THE SEROTONIN 5-HT2A RECEPTOR AND ITS MESSENGER-RNA IN A SUBPOPULATION OF RAT STRIATAL NEURONS

The effects of dopamine receptor agonists on the levels of the striata l serotonin 5-HT2A receptor and its mRNA were investigated in rats les ioned with 6-OHDA as neonates. The mRNA encoding for the 5-HT2A recept or was detected by in situ hybridization histochemistry and the bindin g to 5-HT2A receptors was revealed with [I-125](2,5-dimethoxy-4-iodoph enyl)2-aminopropane ([I-125]DOI). In adult control unlesioned rats, la beling with the 5-HT2A cRNA probe and with [I-125]DOI was concentrated in medial sectors of the striatum. In 6-OHDA-lesioned rats, labeling with the 5-HT2A cRNA probe or with [I-125]DOI was increased in the str iatum, particularly in its lateral subdivisions, These increases were abolished after chronic systemic administration of the dopamine recept or 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 wa s distributed in PPE-labeled as well as in PPE-unlabeled striatal neur ons. 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 o f dopamine receptors inhibit the expression of 5-HT2A receptors in a s ubpopulation 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.