Volume 16, Number 11,
Issue of June 1, 1996
pp. 3727-3736
Copyright ©1996 Society for Neuroscience
Dopamine Receptor Agonists Regulate Levels of the Serotonin
5-HT2A Receptor and its mRNA in a Subpopulation of Rat
Striatal Neurons
Received Jan. 19, 1996; revised March 6, 1996; accepted March 8, 1996.
Nathalie Laprade1,
Fatiha Radja2,
Tomás A. Reader2, 3, and
Jean-Jacques Soghomonian1
1 Centre de Recherche en Neurobiologie and
Département d'Anatomie, Faculté de Médecine,
Université Laval, Québec, Canada, and Départements de
2 Physiologie et 3 Psychiatrie, Faculté
de Médecine, Université de Montréal,
Québec, Canada
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 to
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.
Key words:
striatum;
5-HT;
dopamine;
6-OHDA;
5-HT2A
serotonin receptor;
D1 dopamine receptor