Conditioned place aversion induced by 5-HT(1C) receptor antagonists.
A place-conditioning procedure was used to investigate the affective properties in rats of non-selective serotonin receptor antagonists (mianserin, eltoprazine and ketanserin) differing from each other by their affinity for 5-HT(1C) and 5-HT(2) receptors among others. At the highest dose tested (10mg/kg,i.p.), the mixed 5-HT(1C)/5-HT(2) receptor antagonist mainserin produced a significant place aversion to the drug-paired compartment. The 5-HT(1B) receptor agonist/5-HT(1C) receptor antagonist eltoprazine induced a place aversion at doses of 1 and 10mg/kg. In contrast, the 5-HT(2) receptor antagonist ketanserin produced neither place aversion nor place preference at the doses tested (1 or 10mg/kg, i.p.). The preferential 5-HT(1C) receptor agonist mCPP was given prior to mianserin or eltoprazine administration. mCPP (1mg/kg, i.p.) significantly prevented the conditioned place aversion produced by mianserin or eltoprazine, without exhibiting any aversive or rewarding effect by itself. These results suggest that acute 5-HT(1C) receptor blockade is involved in the production of aversive effects of mianserin and eltoprazine.
Rocha
B.
B
Laboratoire de Neurophysiologie et Biologie des Comportements, 5, rue Blaise Pascal F67084, Strasbourg, France.
Di Scala
G.
G
Jenck
F.
F
Moreau
J.-L.
JL
Sandner
G.
G