SEROTONIN

Evaluate the Proposition That Decreases in Serotonin Will Impair Working Memory & Executive Function With Reference To both Human and Animal Models

Evaluate the Proposition That Decreases in Serotonin Will Impair Working Memory & Executive Function With Reference To both Human and Animal Models

Introduction

Serotonin (5-hydroxytryptamine, 5-HT) is widely distributed in the whole brain and plays a role in a great variety of behaviours such as activity rythms, food intake, sexual behaviour and emotional states. Selective serotonin reuptake inhibitors (SSRI), eg fluoxetine, are widely used as antidepressants. This variety suggests a lack of functional specialization. However, there is increasing evidence showing that 5- HT is associated with cognitive functions, especially learning, memory and attentional processes (Buhot, 1997, 243-54). These functions are not independent from each other or from other behavioural levels. For example, there are some connections between anxiety and memory, or between memory and attentional processes. It is thus clear that 5-HT may modulate learning and memory by both direct and indirect ways. If memory functions are mainly and more directly controlled by other neurotransmission systems, such as the cholinergic or the glutamatergic ones, it is presently clear that by interacting with these systems, 5-HT and its various receptors play an important role in learning and memory. This study also presents recent scientific arguments supporting this view, in particular in cases in which these functions are deficient, ie in memory impairment. Study will focus on the functional relationship of the behavioural and neurobiological levels to provide a better understanding of the neuronal mechanisms underlying learning and memory.

Soubrik (1997, pp.319-64) suggested that the primary function of serotonergic neurotransmission was to inhibit ongoing behaviour. Thus, reducing 5-HT transmission was found to induce impulsivity, ie it made animals less tolerant to the delay of positive reinforcement (Wogar, Bradshaw, Szabadi 1993, 239-43). Decreasing the level of 5-HT in the brain results in a general response disinhibition, increasing thus resistance to extinction (Beninger, Phillips 1979, 37-41), ie the inability to disconnect previously formed associations, preventing thus the subject from forming new associations, ie from new learning. Reducing central 5-HT synthesis through L-tryptophan restriction impairs specifically short-term and long-term memory performance in rats and humans. Some studies, however, did not reveal any effect on rat learning performance with such treatment administered either acutely or chronically (Stancampiano et al. 1997, 269-74). At the neurobiological level, depletion of 5-HT (by using the tryptophan hydroxylase inhibitor, parachlorophenylalanine, pCPA) during synaptogenesis decreases synaptic density in the adult rat hippocampus thus inducing spatial learning deficits associated with failure of extinction and consequently failure of relearning. A recent work demonstrated that depletion in 5-HT also decreases the number of newly generated cells in the rat hippocampus. However, 5-HT depletion following 5,7-dihydroxytryptamine (DHT) lesioning has been found to induce facilitatory effects on acquisition and performance of various learning tasks in rats, such as spatial discrimination, conditional visual discrimination, presumably by reducing proactive interference, and temporal discrimination under certain conditions, eg when the difficulty of the task is ...