Reduced activity at the 5-HT(2C) receptor enhances reversal learning by decreasing the influence of previously non-rewarded associations.
BACKGROUND
Reversal learning deficits are a feature of many human psychopathologies and their associated animal models and have recently been shown to involve the 5-HT(2C) receptor (5-HT(2C)R). Successful reversal learning can be reduced to two dissociable cognitive mechanisms, to dissipate associations of previous positive (opposed by perseverance) and negative (opposed by learned non-reward) valence.


OBJECTIVE
This study aims to explore the effect of reducing activity at the 5-HT(2C)R on the cognitive mechanisms underlying spatial reversal learning in the mouse.


METHODS
Experiment 1 used the 5-HT(2C)R antagonist SB242084 (0.5 mg/kg) in a between-groups serial design, experiment 2 used 5-HT(2C)R KO mice in a repeated measures design. Animals initially learned to discriminate between two lit nosepoke holes. This was followed by three conditions; (1) full reversal, where contingencies reversed; (2) perseverance, where the previous CS+ became CS- and the previous CS- was replaced by a novel CS+; (3) learned non-reward, where the previous CS- became CS+ and the previous CS+ was replaced by a novel CS-.


RESULTS
SB242084 treated and 5-HT(2C)R KO mice showed enhanced reversal learning seen as a decrease in trials, correct responses, and omissions to criterion in the full reversal condition. Similar effects were observed in the learned non-reward condition but SB242084 treated and 5-HT(2C)R KO mice did not differ from controls in the perseverance condition. SB242084 treated, but not 5-HT(2C)R KO mice, showed decreases in all latency indices in every condition.


CONCLUSIONS
Reducing activity at the 5-HT(2C)R facilitates reversal learning in the mouse by reducing the influence of previously non-rewarded associations.
School of Psychology, University of Sussex, Brighton, BN1 9QH, UK. s.nilsson@sussex.ac.uk
S R O
SR
Nilsson
T L
TL
Ripley
E M
EM
Somerville
P G
PG
Clifton
D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012193:Reversal Learning / Q000187:drug effects*; D012201:Reward; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology*; D013997:Time Factors
C107820:6-chloro-5-methyl-1-((2-(2-methylpyrid-3-yloxy)pyrid-5-yl)carbamoyl)indoline; D000631:Aminopyridines; D007211:Indoles; D044405:Receptor, Serotonin, 5-HT2C; D058830:Serotonin 5-HT2 Receptor Antagonists