Pro-cognitive effects of 5-HT6 receptor antagonists in the social recognition procedure in rats: implication of the frontal cortex.
BACKGROUND
5-HT6 receptor antagonists improve cognitive processes in rodents. However, their site(s) of action remains unexplored and their influence upon social memory has been little investigated.


OBJECTIVE
We examined the influence of 5-HT6 receptor ligands upon social memory in rats by use of systemic or local administration into the frontal cortex (FCX), striatum, or nucleus basalis magnocellularis (NBM).


METHODS
The social recognition test is based upon the ability of an adult rat to recognize a younger conspecific during the second of two 5-min sessions. In a procedure without an inter-session interval, the actions of drugs alone and the ability to reverse "amnesia" induced by the muscarinic antagonist, scopolamine (1.25 mg/kg, s.c.), were examined. The potential promnesic effect of drugs was also investigated in another procedure where a spontaneous deficit of recognition was induced by a 120-min inter-session interval.


RESULTS
The 5-HT6 receptor agonist, WAY-181187 (10.0 mg/kg, i.p.), significantly impaired social recognition. This effect was abolished by the 5-HT6 receptor antagonists, SB-271046 (20.0 mg/kg, i.p.) and SB-258585 (10.0 mg/kg, i.p.). These agents also abolished scopolamine-induced amnesia (10.0 and 2.5 mg/kg, i.p., respectively) and reversed the delay-induced deficit (10.0-20.0 and 2.5-10.0 mg/kg, i.p., respectively). WAY-181187 into the FCX significantly impaired social recognition (0.16-0.63 microg/side). Conversely, SB-271046 into the FCX (2.5-5.0 microg/side), but neither into the striatum nor the NBM, significantly reversed spontaneous deficit.


CONCLUSIONS
These results indicate that 5-HT6 receptors modulate social recognition by actions in the FCX and underpin their pertinence as targets for the treatment of psychiatric disorders in which cognitive function is compromised.
Loiseau
Florence
F
Department of Psychopharmacology, Institut de Recherches Servier, 125 Chemin de ronde, 78290, Croissy-sur-Seine, Paris, France.
Dekeyne
Anne
A
Millan
Mark J
MJ
D000818:Animals; D020532:Basal Nucleus of Meynert / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000187:drug effects*; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D008845:Microinjections; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D012601:Scopolamine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D012919:Social Behavior; D013449:Sulfonamides / Q000494:pharmacology*; D013876:Thiophenes / Q000494:pharmacology*
D010879:Piperazines; D011985:Receptors, Serotonin; C418570:SB 258585; D012702:Serotonin Antagonists; D013449:Sulfonamides; D013876:Thiophenes; C097216:serotonin 6 receptor; D012601:Scopolamine; C117443:SB 271046