Role of serotonin in memory impairment

Buhot, Marie-Christine; Martin, Stéphanie; Ségu, Louis

doi:10.3109/07853890008998828

Cited by 372 publications

(229 citation statements)

References 117 publications

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“…The role of the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) in learning and memory has been demonstrated in both humans and animals (Buhot 1997;Buhot et al 2000;Meneses 1999;Riedel et al 1999;Schmitt et al 2000). Studies using the method of acute tryptophan depletion (ATD), which results in lower peripheral and central levels of tryptophan and 5-HT Fernstrom and Wurtman 1997;Gessa et al 1974;Moja et al 1989;Stancampiano et al 1997), consistently report impaired memory in healthy volunteers (Park et al 1994;Riedel et al 1999;Sambeth et al 2007;Schmitt et al 2000) and rats (Jans et al 2007a;Lieben et al 2004b;Rutten et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

et al. 2008

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Rationale Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats. Objectives As individual differences exist in central serotonin neurotransmission, the impact of ATD may vary accordingly. In this experiment, we investigated the hypothesis that male serotonin transporter knockout (SERT −/− ), rats marked by a lower SERT function, are more vulnerable to the effects of ATD in an object recognition task than male wildtype (SERT +/+ ) and heterozygous (SERT +/− ) rats. Materials and methods Twelve male SERT +/+ , SERT +/− , and SERT −/− rats were treated with standard dose and lowdose ATD using a gelatine-based protein-carbohydrate mixture lacking tryptophan. In the control treatment, Ltryptophan was added to the mixture. Four hours after treatment, the rats were subjected to the object recognition task. In addition, the effects of ATD on plasma amino acid concentrations were measured, and concentrations of 5-HT and 5-HIAA were measured in the frontal cortex and hippocampus of these rats. Results Plasma TRP levels and central 5-HT and 5-HIAA levels were decreased in all genotypes after ATD, but effects were stronger in SERT −/− rats. The standard dose of ATD impaired object recognition in all genotypes. SERT −/− and SERT +/− rats were more vulnerable to low dose of ATD in the object recognition task compared to SERT +/+ rats. Conclusions These results indicate a greater sensitivity to ATD in SERT −/− and SERT +/− rats, which may be related to stronger central depletion effects in these rats.

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Section: Introductionmentioning

confidence: 99%

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

et al. 2008

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“…The use of selective serotonin agonists and antagonists has increased our understanding of the role of 5-HT receptors in processes of learning and memory (Barnes et al, 1992;Buhot et al, 2000). Recently, serotonin type 6 (5-HT 6 ) receptors were shown to be targets for cognitive-enhancing drugs (Meneses, 1999).…”

Section: Introductionmentioning

confidence: 99%

The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

Lieben

Blokland

Şık

et al. 2005

Neuropsychopharmacol

135

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Antagonists at serotonin type 6 (5-HT 6 ) receptors show activity in models of learning and memory. Although the underlying mechanism(s) are not well understood, these effects may involve an increase in acetylcholine (ACh) levels. The present study sought to characterize the cognitive-enhancing effects of the 5-HT 6 antagonist Ro4368554 (3-benzenesulfonyl-7-(4-methyl-piperazin-1-yl)1H-indole) in a rat object recognition task employing a cholinergic (scopolamine pretreatment) and a serotonergic-(tryptophan (TRP) depletion) deficient model, and compared its pattern of action with that of the acetylcholinesterase inhibitor metrifonate. Initial testing in a time-dependent forgetting task employing a 24-h delay between training and testing showed that metrifonate improved object recognition (at 10 and 30 mg/kg, p.o.), whereas Ro4368554 was inactive. Both, Ro4368554 (3 and 10 mg/kg, intraperitoneally (i.p.)) and metrifonate (10 mg/kg, p.o., respectively) reversed memory deficits induced by scopolamine and TRP depletion (10 mg/kg, i.p., and 3 mg/kg, p.o., respectively). In conclusion, although Ro4368554 did not improve a time-related retention deficit, it reversed a cholinergic and a serotonergic memory deficit, suggesting that both mechanisms may be involved in the facilitation of object memory by Ro4368554 and, possibly, other 5-HT 6 receptor antagonists.

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“…At the same time, several lines of evidence point to a role for 5-HT in memory (Buhot et al, 2000). Most prominently, depletion of tryptophan (TRP), a precursor of 5-HT, is associated with lower performance on episodic memory retention tests in humans (Riedel et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Effects of 5-HT on Memory and the Hippocampus: Model and Data

Meeter

Talamini

Schmitt

et al. 2005

Neuropsychopharmacol

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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-HT 1A and 5-HT 3 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-HT 1A agonists ameliorate memory deficits in depression. INTRODUCTIONHypofunction of the 5-hydroxytryptamine (5-HT) system has emerged as a leading candidate cause for depression (Naughton et al, 2000;Middlemiss et al, 2002). At the same time, several lines of evidence point to a role for 5-HT in memory (Buhot et al, 2000). Most prominently, depletion of tryptophan (TRP), a precursor of 5-HT, is associated with lower performance on episodic memory retention tests in humans (Riedel et al, 1999). This mirrors findings in depression, which is accompanied by moderate to severe memory deficits (Johnson and Magaro, 1987;Schaub et al, 2003). However, manipulations that increase 5-HT concentration or 5-HT receptor activation also lower memory performance, as indicated by receptor agonist studies in both humans (Riedel et al, 2002) and animals (Altman and Normile, 1988). Up to now, it is not known why both increased and decreased 5-HT activation have adverse effects on memory.5-HT binds to a large and disparate family of CNS receptors, which have effects that are sometimes opposite. Thus, many effects of different receptors seem to cancel each other out. In a review (see Supplementary Information on internet), we identify two robust effects of 5-HT in the hippocampus. First, 5-HT exerts a hyperpolarizing influence on principal cells; directly, via 5-HT 1A receptors, and indirectly, via facilitation of GABA release from local interneurons through 5-HT 3 receptors (Burnet et al, 1995;Piguet and Galvan, 1994). Activation of 5-HT 2A and 5-HT 2C receptors has been suggested to induce depolarization in principal cells (Piguet and Galvan, 1994;Barnes and Sharp, 1999), but these effects appear to be dominated by the depolarizing effects of 5-HT, as bath application of 5-HT will hyperpolarize principal cells in slice preparations of the dentate gyrus (Piguet and Galvan, 1994). In addition, through 5-HT 2C , 5-HT 4 , and 5-HT 7 receptors, afterhyperpolarizing (AHP) currents are downregulated, leading to reduced adaptation in principal cells (Torres et al, 1996;Bac...

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Role of serotonin in memory impairment

Cited by 372 publications

References 117 publications

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

Acute tryptophan depletion dose dependently impairs object memory in serotonin transporter knockout rats

The Selective 5-HT6 Receptor Antagonist Ro4368554 Restores Memory Performance in Cholinergic and Serotonergic Models of Memory Deficiency in the Rat

Effects of 5-HT on Memory and the Hippocampus: Model and Data

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