Diverse effects of 5-HT2C receptor blocking agents on c-Fos expression in the rat basal ganglia.
Serotonin(2C) receptors (5-HT(2)C) exert continuous control on the activity of specific populations of neurons in the basal ganglia. While antagonists block the effect of endogenous 5-HT at 5-HT(2C) receptors, the actions of inverse agonists may also involve interruption of activity at constitutively active populations of 5-HT(2C) receptors. We have evaluated the regional impact of these controls by studying, in rats, the expression of the product of the proto-oncogene c-Fos in rat basal ganglia after peripheral doses of the 5-HT(2C) antagonist SB 243213 (5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline) and the 5-HT(2B/2C) inverse agonists SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole.hydrochloride) and S32006 (N-pyridin-3-yl-1,2-dihydro-3H-benzo[e]indole-3-carboxamide). The results show that 1 and 10mg/kg SB 243213 enhanced equally c-Fos expression in the subthalamic nucleus (STN) and dose-dependently in the striatum and nucleus accumbens core (NAcc). SB 206553 (1-10mg/kg), at 10mg/kg only, enhanced c-Fos expression in STN, striatum (except the dorsomedial part), NAcc, entopeduncular nucleus, substantia nigra pars reticulata (SNr) and compacta (SNc) and ventral tegmental area. S32006 induced a similar increase in c-Fos expression in the medial parts of the striatum and NAcc at doses of 1-10mg/kg while it dose-dependently enhanced c-Fos expression in medial parts of the STN and SNr. None of these drugs induced c-Fos expression in the globus pallidus. The distinct pattern of c-Fos expression elicited by the 5-HT(2C) antagonist and inverse agonists suggests the existence of cellular and functional heterogeneity in the response of the basal ganglia to drugs inhibiting 5-HT(2C) receptors.
Unité Mixte de Recherche-Centre National de la Recherche Scientifique (UMR-CNRS) 5293, Institut des Maladies Neurodégénératives, Université de Bordeaux, 146 rue Léo Saignat, B.P.281, 33076 Bordeaux Cedex, France.
Nabila
N
Kadiri
Mélanie
M
Lagière
Catherine
C
Le Moine
Mark J
MJ
Millan
Philippe
P
De Deurwaerdère
Sylvia
S
Navailles
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*
D016760:Proto-Oncogene Proteins c-fos; D058830:Serotonin 5-HT2 Receptor Antagonists