Serial reversal learning and acute tryptophan depletion.

Cognitive flexibility (i.e. the ability to adapt goal-directed behaviour in response to changed environmental demands) has repeatedly been shown to depend on the prefrontal cortex (PFC). Recent data from primate studies moreover show that depletion of prefrontal 5-HT impairs reversal learning of visual stimuli [Clarke HF, Walker SC, Crofts HS, Dalley JW, Robbins TW, Roberts AC. Prefrontal serotonin depletion affects reversal learning but not attentional set shifting. J Neurosci 2005;25:532-8; Clarke HF, Walker SC, Dalley JW, Robbins TW, Roberts AC. Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific. Cereb Cortex 2007;17:18-27]. It is not clear however if 5-HT serves a general role in reversal learning or if it is involved only in specific reversal problems. A first aim of these experiments was to study the role of 5-HT in serial reversal learning of a spatial discrimination. Literature has, moreover, repeatedly shown that the PFC is involved in the initial acquisition of a reversal problem but hardly when the task is well practiced. A second aim concerns the role of 5-HT in early versus late reversal learning. With the current experiment, we aim to clarify whether 5-HT is differentially involved in early versus late reversal learning. To this end, we tested rats on a serial two-lever reversal task and induced a temporary reduction of 5-HT availability in these rats by restricting dietary intake of the 5-HT precursor tryptophan at an early and a late reversal. Our results indicate that acute tryptophan depletion (ATD) did not affect either early or late reversal learning, nor extinction and suggest that spatial reversal learning, in contrast to visual reversal learning, might not be dependent on 5-HT. The data furthermore provide insight in the behavioural strategies employed in serial reversal learning and suggests the formation of a learning-set.