Reduced activity at the [5-HT.sub.2C] receptor enhances reversal learning by decreasing the influence of previously non-rewarded associations

Rationale 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.sub.2C] receptor ([5-HT.sub.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. Objectives This study aims to explore the effect of reducing activity at the [5-HT.sub.2C]R on the cognitive mechanisms underlying spatial reversal learning in the mouse. Methods Experiment 1 used the [5-HT.sub.2C]R antagonist SB242084 (0.5 mg/kg) in a between-groups serial design, experiment 2 used [5-HT.sub.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.sub.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.sub.2C]R KO mice did not differ from controls in the perseverance condition. SB242084 treated, but not [5-HT.sub.2C]R KO mice, showed decreases in all latency indices in every condition. Conclusion Reducing activity at the [5-HT.sub.2C]R facilitates reversal learning in the mouse by reducing the influence of previously non-rewarded associations. Keywords Reversal learning * SB242084 * [5-HT.sub.2C]KO * [5-HT.sub.2C] receptor * Serotonin * Perseverance * Learned non-reward