Serotonin modulates sensitivity to reward and negative feedback in a probabilistic reversal learning task in rats

Andrea Bari (1) , David Edward Harry Theobald (1) , Daniele Caprioli (1) , Adam C Mar (1) , Alex Aidoo-Micah (1) , Jeffrey W. Dalley (1) , Trevor W Robbins (1)

1 Experimental Psychology

Depressed patients show cognitive deficits that may depend on an abnormal reaction to positive and negative feedback. The precise neurochemical mechanisms responsible for such cognitive abnormalities have not yet been clearly characterized, although serotoninergic dysfunction is frequently associated with depression. In three experiments described here, we investigated the effects of different manipulations of central serotonin (5-HT) levels in rats performing a probabilistic reversal learning task which measures response to feedback. Increasing or decreasing 5-HT tone differentially affected behavioral indices of cognitive flexibility (reversals completed), reward sensitivity (win-stay) and reaction to negative feedback (lose-shift). A single low dose of the selective serotonin reuptake inhibitor (SSRI) citalopram (1 mg/kg) resulted in fewer reversals completed and increased lose-shift behavior. By contrast, a single higher dose of citalopram (10 mg/kg) exerted the opposite effect on both measures. Repeated (5 mg/kg, daily, seven days) and sub-chronic (10 mg/kg, i.b.d., five days) administration of citalopram increased the number of reversals completed by the animals and increased the frequency of win-stay behavior, while global 5-HT depletion had the opposite effect on both indices. These results show that boosting 5-HT neurotransmission decreases negative feedback sensitivity and increases reward (positive feedback) sensitivity, while reducing it has the opposite effect. However, these effects depend on the nature of the manipulation used: acute manipulations of the 5-HT system modulate negative feedback sensitivity, while long-lasting treatments specifically affect reward sensitivity. The results parallel some of the findings in humans on effects of 5-HT manipulations and are relevant to hypotheses of altered response to feedback in depression.

Mots clés: Serotonin; Depression; Unipolar/Bipolar; Psychopharmacology; Behavioral Science; Citalopram; Probabilistic reversal learning

Andrea Bari, David Edward Harry Theobald, Daniele Caprioli, Adam C Mar, Alex Aidoo-Micah, et al.. Serotonin modulates sensitivity to reward and negative feedback in a probabilistic reversal learning task in rats. Neuropsychopharmacology, 2010, n/a (n/a), pp.n/a-n/a. ⟨10.1038/npp.2009.233⟩. ⟨hal-00506037⟩