A comparative study of the effects of selective and non-selective 5-HT2 receptor subtype antagonists in rat and mouse models of anxiety.
Although there is some evidence that compounds acting at 5-HT2 receptors show anxiolytic activity, little is known about the specific involvement of the different 5-HT2 receptor subtypes in the modulation of anxiety-related responses. In the present study, the behavioural effects of mianserin, a non-selective 5-HT2 receptor antagonist, MDL 100,907, a selective 5-HT2A receptor antagonist, and SB 206553, a selective 5-HT2B/2C receptor antagonist, were investigated in two rat (the Vogel drinking conflict and the elevated plus-maze tests) and two mouse (i.e. the mouse defense test battery (MDTB) and the light/dark choice test) models of anxiety. Diazepam was used as a positive control. In the Vogel drinking test, mianserin (10 mg/kg) and SB 206553 (3-30 mg/kg), but not MDL 100,907, increased punished responding. Similarly, mianserin (1 mg/kg) and SB 206553 (3-10 mg/kg), but not MDL 100,907, increased entries into the open arms of the elevated plus-maze. These effects are consistent with anxiolytic-like actions of mianserin and SB 206553, although the magnitude of the effects of these two compounds was less than those of diazepam. In addition, in the MDTB, the 5-HT2 antagonists did not clearly affect the defensive reactions of mice exposed to a rat stimulus and they failed to reverse the avoidance of the illuminated box in the light/dark choice test. These results indicate a lack of anxiolytic-like action of the compounds in mice. These behavioural profiles suggest that blockade of the 5-HT2A receptor may not reduce anxiety and demonstrate that 5-HT2B and/or 5-HT2C receptor subtypes may be primarily involved in the anxiolytic-like effects of mianserin and SB 206553 in rats.
Griebel
G
G
CNS Research Department, Synthélabo Recherche, Bagneux, France. ggriebel@compuserve.com
Perrault
G
G
Sanger
D J
DJ
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001007:Anxiety / Q000503:physiopathology*; D001522:Behavior, Animal / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D005464:Fluorobenzenes / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008803:Mianserin / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000187:drug effects*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D005464:Fluorobenzenes; D007211:Indoles; D010880:Piperidines; D011725:Pyridines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D008803:Mianserin; C094868:SB 206553; C079049:volinanserin; D003975:Diazepam