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5-Hydroxytryptamine (5-HT) transmission has been implicated in memory and in depression. Both 5-HT depletion and specific 5-HT agonists lower memory performance, while depression is also associated with memory deficits. The precise neuropharmacology and neural mechanisms underlying these effects are unknown. We used neural network simulations to elucidate the neuropharmacology and network mechanisms underlying 5-HT effects on memory. The model predicts that these effects are largely dependent on transmission over the 5-HT1A and 5-HT3 receptors, which regulate the selectivity of retrieval. It also predicts differential memory deficit profiles for 5-HT depletion and overactivation. The latter predictions were confirmed in studies with healthy and depressed participants undergoing acute tryptophan depletion or ipsipirone challenge. The results suggest that the memory impairments in depressed subjects may be related to 5-HT undertransmission, and support the notion that 5-HT1A agonists ameliorate memory deficits in depression.Neuropsychopharmacology (2006) 31, 712–720. doi:10.1038/sj.npp.1300869; published online 31 August 2005 [ABSTRACT FROM AUTHOR]

It has frequently been demonstrated that acute tryptophan depletion (ATD) induces a transient depressed mood in some patients who are in remission from depression. However, the effects of ATD on cognitive processes in remitted depressed patients have not been investigated. The aim of the present study was to investigate the effects of different extents of depletion on mood and cognitive tasks involving neutral and emotional stimuli. Twenty patients in remission or in partial remission from depression received ATD in a double-blind, crossover design. Mood was assessed at both sessions before, at +6.5 h and +24 h after depletion. Cognitive assessment in both sessions started at +4.75 h, and also before and after the whore procedure. The ATD mixtures induced the expected reductions of plasma tryptophan levels. High-dose ATD induced a depressive response in a subsample of patients and impaired the processing of positive information independent of mood change. Attention for neutral stimuli (Stroop interference) improved in a dose-dependent manner. ATD may affect mood and cognition via different pathways: one implicated in mood regulation and the processing of emotional information, and one for the processing of neutral information. The first pathway may be more important for discriminating vulnerability to impaired serotonin function. The comparison of the effects of high-dose and low-dose ATD is useful for those studies aiming to investigate the relationships among 5-HT, mood and cognition. [ABSTRACT FROM AUTHOR]