Serotonin transporter and memory

Depto. de Farmacobiología, CINVESTAV-IPN, Tenorios 235, Granjas Coapa, Mexico City 14330, Mexico.
Neuropharmacology (Impact Factor: 5.11). 09/2011; 61(3):355-63. DOI: 10.1016/j.neuropharm.2011.01.018
Source: PubMed


The serotonin transporter (SERT) has been associated to diverse functions and diseases, though seldom to memory. Therefore, we made an attempt to summarize and discuss the available publications implicating the involvement of the SERT in memory, amnesia and anti-amnesic effects. Evidence indicates that Alzheimer's disease and drugs of abuse like d-methamphetamine (METH) and (+/-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") have been associated to decrements in the SERT expression and memory deficits. Several reports have indicated that memory formation and amnesia affected the SERT expression. The SERT expression seems to be a reliable neural marker related to memory mechanisms, its alterations and potential treatment. The pharmacological, neural and molecular mechanisms associated to these changes are of great importance for investigation.

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Available from: Georgina Perez, May 05, 2014
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    • "Besides deficits in NOR, these studies in rats revealed significant deficits in SERT density in the hippocampus and PRh (Belcher et al., 2008; Reichel et al., 2012). Both clinical and preclinical evidence suggests that cortical and hippocampal SERT sites are important for learning and memory (Meneses et al., 2011 for review). Furthermore, preclinical evidence suggests a link between SERT sites and NOR. "
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    ABSTRACT: Previous studies have demonstrated that methamphetamine (METH) abuse leads to memory deficits and these are associated with relapse. Furthermore, extensive evidence indicates that nicotine (NIC) prevents and/or improves memory deficits in different models of cognitive dysfunction and these nicotinic effects might be mediated by hippocampal or cortical nicotinic acetylcholine receptors (nAChRs). The present study investigated whether NIC attenuates METH-induced novel object recognition (NOR) deficits in rats and explored potential underlying mechanisms. Adolescent or adult male Sprague-Dawley rats received either NIC water (10-75 μg/ml) or tap water for several weeks. METH (4 x 7.5 mg/kg/injection) or saline was administered either before or after chronic NIC exposure. Novel object recognition was evaluated 6 d after METH or saline. Serotonin transporter function and density, and α4β2 nAChR density were assessed on the following day. Chronic NIC intake via drinking water beginning during either adolescence or adulthood attenuated the NOR deficits caused by a high-dose METH administration. Similarly, NIC attenuated METH-induced deficits in NOR when administered after METH treatment. However, NIC did not attenuate the serotonergic deficits caused by METH in adults. Conversely, NIC attenuated METH-induced deficits in α4β2 nAChR density in the hippocampal CA1 region. Furthermore, NIC increased α4β2 nAChR density in the hippocampal CA3, dentate gyrus and perirhinal cortex (PRh) in both saline- and METH-treated rats. Overall, these findings suggest that NIC-induced increases in α4β2 nAChRs in the hippocampus and PRh might be one mechanism by which NOR deficits are attenuated by NIC in METH-treated rats. © The Author 2015. Published by Oxford University Press on behalf of CINP.
    The International Journal of Neuropsychopharmacology 07/2015; DOI:10.1093/ijnp/pyv073 · 4.01 Impact Factor
    • "In this context, reduced marble burying behavior observed in adult SERT −/− mice might be explained by a passive coping strategy in response to environmental stimuli. Previous studies have demonstrated that genetic or pharmacological manipulations of SERT improve memory performance and reversal learning in rodents (Brigman et al. 2010; Meneses et al. 2011; Nonkes et al. 2013). In addition, human evidence has shown that the short promoter variant of the SERT gene might be associated with superiority in some aspects of cognitive function, including decision-making and reversal learning (Crisan et al. 2009; Homberg and Lesch 2011; Homberg et al. 2008). "
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    ABSTRACT: A promoter variant of the serotonin transporter (SERT) gene is known to affect emotional and cognitive regulation. In particular, the "short" allelic variant is implicated in the etiology of multiple neuropsychiatric disorders. Heterozygous (SERT(+/-)) and homozygous (SERT(-/-)) SERT mutant mice are valuable tools for understanding the mechanisms of altered SERT levels. Although these genetic effects are well investigated in adulthood, the developmental trajectory of altered SERT levels for behavior has not been investigated. We assessed anxiety-like and cognitive behaviors in SERT mutant mice in early adolescence and adulthood to examine the developmental consequences of reduced SERT levels. Spine density of pyramidal neurons was also measured in corticolimbic brain regions. Adult SERT(-/-) mice exhibited increased anxiety-like behavior, but these differences were not observed in early adolescent SERT(-/-) mice. Conversely, SERT(+/-) and SERT(-/-) mice did display higher spontaneous alternation during early adolescence and adulthood. SERT(+/-) and SERT(-/-) also exhibited greater neuronal spine densities in the orbitofrontal but not the medial prefrontal cortices. Adult SERT(-/-) mice also showed an increased spine density in the basolateral amygdala. Developmental alterations of the serotonergic system caused by genetic inactivation of SERT can have different influences on anxiety-like and cognitive behaviors through early adolescence into adulthood, which may be associated with changes of spine density in the prefrontal cortex and amygdala. The altered maturation of serotonergic systems may lead to specific age-related vulnerabilities to psychopathologies that develop during adolescence.
    Psychopharmacology 04/2014; 231(21). DOI:10.1007/s00213-014-3554-x · 3.88 Impact Factor
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    • "Therefore, deficits in both synthesis and uptake of serotonin will noticeably influence the thermotaxis memory behavior in C. elegans. Previous studies have implied that the serotonin transporter expression seems to be a reliable neuronal marker related to memory mechanisms, its alterations and potential treatment [28]. In addition, it was reported that human serotonin transporter polyadenylation polymorphism can modulate the retention of fear extinction memory [29]. "
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    ABSTRACT: Caenorhabditis elegans is as an ideal model system for the study of mechanisms underlying learning and memory. In the present study, we employed C. elegans assay system of thermotaxis memory to investigate the possible role of serotonin neurotransmitter in memory control. Our data showed that both mutations of tph-1, bas-1, and cat-4 genes, required for serotonin synthesis, and mutations of mod-5 gene, encoding a serotonin reuptake transporter, resulted in deficits in thermotaxis memory behavior. Exogenous treatment with serotonin effectively recovered the deficits in thermotaxis memory of tph-1 and bas-1 mutants to the level of wild-type N2. Neuron-specific activity assay of TPH-1 suggests that serotonin might regulate the thermotaxis memory behavior by release from the ADF sensory neurons. Ablation of ADF sensory neurons by expressing a cell-death activator gene egl-1 decreased the thermotaxis memory, whereas activation of ADF neurons by expression of a constitutively active protein kinase C homologue (pkc-1(gf)) increased the thermotaxis memory and rescued the deficits in thermotaxis memory in tph-1 mutants. Moreover, serotonin released from the ADF sensory neurons might act through the G-protein-coupled serotonin receptors of SER-4 and SER-7 to regulate the thermotaxis memory behavior. Genetic analysis implies that serotonin might further target the insulin signaling pathway to regulate the thermotaxis memory behavior. Thus, our results suggest the possible crucial role of serotonin and ADF sensory neurons in thermotaxis memory control in C. elegans.
    PLoS ONE 11/2013; 8(11):e77779. DOI:10.1371/journal.pone.0077779 · 3.23 Impact Factor
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