[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: Diverse studies indicate that the attention deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Here SHR-saline group showed significantly poor STM and LTM relative to SD and WKY saline rats. SD and WKY rats treated with d-amphetamine displayed better STM and LTM, compared to SD-vehicle, WKY-vehicle or SHR-d-amphetamine groups.
Behavioural brain research 01/2011; 216(1):472-6. · 3.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growing evidence indicates that antagonists of the 5-hydroxytryptamine (serotonin) receptor6 (5-HT6) improve memory and reverse amnesia, although the mechanisms involved are poorly understood. Hence, in this paper an attempt was made to summarize recent findings. Available evidence indicates that diverse 5-HT6 receptor antagonists produce promnesic and/or antiamnesic effects in diverse conditions, including memory formation, age-related cognitive impairments, memory deficits in diseases such as schizophrenia, Parkinson, and Alzheimer's disease (AD). Notably, some 5-HT6 receptor agonists seem to have promnesic and/or antiamnesic effects. At the present, it is unclear why 5-HT6 receptor agonists and antagonists may facilitate memory or may reverse amnesia in some memory tasks. Certainly, 5-HT6 drugs modulate memory, which are accompanied with neural changes. Likewise, memory, aging, and AD modify 5-HT6 receptors and signaling cascades. Further investigation in different memory tasks, times, and amnesia models together with more complex control groups might provide further clues. Notably, human studies suggest a potential utility of 5-HT6 receptor antagonists in mild-to-moderate AD patients. Even individuals with mild cognitive impairment (MCI) offer a great opportunity to test them.
International Review of Neurobiology 01/2011; 96:27-47. · 2.46 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Diverse studies indicate that attention-deficit hyperactivity disorder (ADHD) is associated with alterations in encoding processes, including working or short-term memory. Some ADHD dysfunctional domains are reflected in the spontaneously hypertensive rat (SHR). Because ADHD, drugs and animal models are eliciting a growing interest, hence the aim of this work is to present a brief overview with a focus on the SHR as an animal model for ADHD and memory deficits. Thus, this paper reviews the concept of SHR as a model system for ADHD, comparing SHR, Wistar-Kyoto and Sprague-Dawley rats with a focus on the hypertension level and working, short-term memory and attention in different behavioral tasks, such as open field, five choice serial reaction time, water maze, passive avoidance, and autoshaping. In addition, drug treatments (d-amphetamine and methylphenidate) are evaluated.
Reviews in the neurosciences 01/2011; 22(3):365-71. · 3.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper deals with the problem of building crack growth models. First, some inconveniences of existing models are described. Next, a general methodology is presented starting by identifying the set of variables involved in the crack growth problem obtaining a minimum subset of dimensionless parameters with the help of the Buckingham theorem, and imposing some consistency and compatibility conditions in terms of functional equations. These functional equations, once solved, provide the subset of crack growth models satisfying the required deterministic and stochastic compatibility conditions, which, in addition to providing mean values of the crack sizes as a function of time, as alternative models do, also give densities of the crack sizes. The main elements required to build a crack growth model, such as the initial crack size distribution, the crack growth function and a loading effect function, have been identified. The methodology is illustrated with some examples, including crack growth for different load histories. Finally, some models proposed in the past are shown to satisfy these conditions and one numerical example is given.
[Show abstract][Hide abstract] ABSTRACT: This paper deals with the problem of building crack growth models and connecting them with Wöhler field models. After, analyzing the physical validity of some crack growth models, a general methodology to build models is presented starting by identifying the set of variables involved in the crack growth problem. Next, a minimum subset of dimensionless parameters using the Buckingham Π theorem is selected. The next step consists of imposing some consistency and compatibility conditions in terms of functional equations, which, once solved, provide the subset of crack growth models satisfying the required deterministic and stochastic compatibility conditions, which, in addition to providing mean values of the crack sizes as a function of time, as alternative models do, also give densities of the crack sizes. As a result, the main elements required to build a crack growth model, such as the initial crack size distribution, the crack growth function and a loading effect functions, have been identified. Finally, the compatibility of Wöhler field and crack growth models is dealt with and the advantages of such a dual treatment is emphasized. The methodology is illustrated with some examples, including crack growth for different load histories, and some conclusions are given.
International Journal of Fatigue 04/2010; 32(4):744-753. · 1.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serotonin transporter (SERT) has been associated with drugs of abuse like d-methamphetamine (METH). METH is well known to produce effects on the monoamine systems but it is unclear how METH affects SERT and memory. Here the effects of METH and the serotonin reuptake inhibitor fluoxetine (FLX) on autoshaping and novel object recognition (NOR) were investigated. Notably, both memory tasks recruit different behavioral, neural and cognitive demand. In autoshaping task a dose-response curve for METH was determined. METH (1.0mg/kg) impaired short-term memory (STM; lasting less of 90min) in NOR and impaired both STM and long-term memory (LTM; lasting 24 and 48h) in autoshaping, indicating that METH had long-lasting effects in the latter task. A comparative autoradiography study of the relationship between the binding pattern of SERT in autoshaping new untrained vs. trained treated (METH, FLX, or both) animals was made. Considering that hemispheric dominance is important for LTM, hence right vs. left hemisphere of the brain was compared. Results showed that trained animals decreased cortical SERT binding relative to untrained ones. In untrained and trained treated animals with the amnesic dose (1.0mg/kg) of METH SERT binding in several areas including hippocampus and cortex decreased, more remarkably in the trained animals. In contrast, FLX improved memory, increased SERT binding, prevented the METH amnesic effect and re-established the SERT binding. In general, memory and amnesia seemed to make SERT more vulnerable to drugs effects.
Behavioural brain research 03/2010; 212(1):12-26. · 3.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growing evidence indicates that 5-hydrohytryptamine (5-HT) receptors mediate learning and memory. Particularly interesting are 5-HT(6) and 5-HT(7) receptors, which are localized in brain areas involved in memory formation. Interestingly, recently selective 5-HT(6) and 5-HT(7) receptor agonists and antagonists have become available. Previous evidence indicates that 5-HT(6) or 5-HT(7) receptors antagonists had no effects, improved memory formation and/or reversed amnesia. Herein, the effects of EMD (a 5-HT(6) receptor agonist) and AS19 (a 5-HT(7) receptor agonist) in the associative learning task of autoshaping were studied. Post-training systemic administration of EMD (1-10 mg/kg) or AS19 (1-10 mg/kg) were tested in short-term memory (STM) and long-term memory (LTM). Results showed that only EMD 5.0mg/kg impaired both STM and LTM. AS19 at 1-10 mg/kg significantly impaired STM but not LTM. In those groups used to test only LTM, EMD impaired it; while AS19 improved LTM. Moreover, in the interaction experiments, the STM EMD-impairment effect was partially reversed by the selective 5-HT(6) receptor antagonist SB-399885 (10 mg/kg). The STM AS19-impairment effect (5.0 mg/kg) was not altered by the selective 5-HT(1A) antagonist WAY 100635 (0.3 mg/kg) but reversed by the selective 5-HT(7) receptor antagonist SB-269970 (10.0 mg/kg). The AS19-SB-269970 combination impaired LTM. Taken together these data suggest that the stimulation of 5-HT(6) impaired both STM and LTM. 5-HT(7) receptors stimulation impaired STM but improved LTM. And these results are discussed in the context of their possible neural bases.
Behavioural brain research 12/2008; 195(1):112-9. · 3.22 Impact Factor
Proceedings of the European Safety and Reliability Conference 2008 (ESREL 2008), Safety, Reliability and Risk Analysis: Theory, Methods and Applications, Edited by Martorel, S, Guedes Solares, C. and Barnett, J, 01/2008: pages 2473-2488; Taylor & Francis Group.
[Show abstract][Hide abstract] ABSTRACT: Traditionally, the search for memory circuits has been centered on examinations of amnesic and AD patients, cerebral lesions and, neuroimaging. A complementary alternative might be the use of autoradiography with radioligands. Indeed, ex vivo autoradiographic studies offer the advantage to detect functionally active receptors altered by pharmacological tools and memory formation. Hence, herein the 5-HT6 receptor antagonist SB-399885 and the amnesic drugs scopolamine or dizocilpine were used to manipulate memory consolidation and 5-HT6 receptors expression was determined by using [3H]-SB-258585. Thus, memory consolidation was impaired in scopolamine and dizocilpine treated groups relative to control vehicle but improved it in SB-399885-treated animals. SB-399885 improved memory consolidation seems to be associated with decreased 5-HT6 receptors expression in 15 out 17 brain areas. Scopolamine or dizocilpine decreased 5-HT6 receptors expression in nine different brain areas and increased it in CA3 hippocampus or other eight areas, respectively. In brain areas thought to be in charge of procedural memory such basal ganglia (i.e., nucleus accumbens, caudate putamen, and fundus striate) data showed that relative to control animals amnesic groups showed diminished (scopolamine) or augmented (dizocilpine) 5-HT6 receptor expression. SB-399885 showing improved memory displayed an intermediate expression in these same brain regions. A similar intermediate expression occurs with regard to amygdala, septum, and some cortical areas in charge of explicit memory storage. However, relative to control group amnesic and SB-399885 rats in the hippocampus, region where explicit memory is formed, showed a complex 5-HT6 receptors expression. In conclusion, these results indicate neural circuits underlying the effects of 5-HT6 receptor antagonists in autoshaping task and offer some general clues about cognitive processes in general.
Behavioural Brain Research 03/2007; 178(1):53-61. · 3.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper presents an integrated approach to sensitivity analysis in some linear and non-linear programming problems. Closed formulas for the sensitivities of the objective function and primal and dual variables with respect to all parameters for some classes of problems are obtained. As particular cases, the sensitivities with respect to all data values, i.e., cost coefficients, constraints coefficients and right hand side terms of the constraints are provided for these classes of problems as closed formulas. The method is illustrated by its application to several examples.
[Show abstract][Hide abstract] ABSTRACT: The paper introduces a new approach to composite breakwater design based on minimizing initial/construction costs subject to yearly failure rate bounds for all failure modes, and presents a technique for sensitivity analysis. The solution of the resulting optimization problem becomes complex because the evaluation of failure rates involves one optimization problem per failure mode (FORM), so that a decomposition method is used to solve the problem. In addition, a sensitivity analysis is performed, which makes it possible to determine how the cost and yearly failure rates of the optimal solution are affected by small changes in the input data values. The proposed method is illustrated by its application to the design of a composite wall under breaking and non-breaking wave conditions. The storms are assumed to be stochastic processes characterized by their maximum significant wave heights, their maximum wave heights and the associated zero-up-crossing mean periods.
[Show abstract][Hide abstract] ABSTRACT: This paper presents a perturbation approach for performing sensitivity analysis of mathematical programming problems. Contrary
to standard methods, the active constraints are not assumed to remain active if the problem data are perturbed, nor the partial
derivatives are assumed to exist. In other words, all the elements, variables, parameters, Karush–Kuhn–Tucker multipliers,
and objective function values may vary provided that optimality is maintained and the general structure of a feasible perturbation
(which is a polyhedral cone) is obtained. This allows determining: (a) the local sensitivities, (b) whether or not partial
derivatives exist, and (c) if the directional derivative for a given direction exists. A method for the simultaneous obtention
of the sensitivities of the objective function optimal value and the primal and dual variable values with respect to data
is given. Three examples illustrate the concepts presented and the proposed methodology. Finally, some relevant conclusions
Journal of Optimization Theory and Applications 12/2005; 128(1):49-74. · 1.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pharmacological evidence indicates a specific role of 5-HT(4) receptors on memory function. These receptors are members of G-protein-coupled 7-transmembrane domain receptor superfamily, are positively coupled to adenylyl cyclase, and are heterogeneously located in some structures important for memory, such as the hippocampus and cortical regions. To further clarify 5-HT(4) receptors' role in memory, the expression of these receptors in passive (P3) untrained and autoshaping (A3) trained (3 sessions) adult (3 months) and old (P9 or A9; 9 months) male rats was determined by autoradiography. Adult trained (A3) rats showed a better memory respect to old trained (A9). Using [(3)H] GR113808 as ligand (0.2 nM specific activity 81 Ci/mmol) for 5-HT(4) receptor expression, 29 brain areas were analyzed, 16 areas of A3 and 17 of A9 animals displayed significant changes. The medial mammillary nucleus of A3 group showed diminished 5-HT(4) receptor expression, and in other 15 brain areas of A3 or 10 of A9 animals, 5-HT(4) receptors were increased. Thus, for A3 rats, 5-HT(4) receptors were augmented in olfactory lobule, caudate putamen, fundus striatum, CA2, retrosplenial, frontal, temporal, occipital, and cingulate cortex. Also, 5-HT(4) receptors were increased in olfactory tubercule, hippocampal CA1, parietal, piriform, and cingulate cortex of A9. However, hippocampal CA2 and CA3 areas, and frontal, parietal, and temporal cortex of A9 rats, expressed less 5-HT(4) receptors. These findings suggest that serotonergic activity, via 5-HT(4) receptors in hippocampal, striatum, and cortical areas, mediates memory function and provides further evidence for a complex and regionally specific regulation over 5-HT receptor expression during memory formation.
Brain Research 05/2005; 1042(1):73-81. · 2.83 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Serotonin (5-hydroxytryptamine, 5-HT) system displays more than 14 receptors subtypes on brain areas involved in learning and memory processes, and pharmacological manipulation of specific receptors selectively affects memory formation. In order to begin the search of 5-HT receptors expression during memory formation, in this work, we aimed to determine, by autoradiography (using [3H] 5-HT as ligand, 2nM, specific activity 123Ci/mmol), 5-HT receptors (5-HTR) expression in passive (untrained) and autoshaping trained (3 sessions) adult (3 months) and old (9 months) male rats. Thus, trained adult rats had better retention than old animals. Raphe nuclei of adult and old trained rats expressed less receptors on medial and dorsal, respectively. Hippocampal CA1 area and dentate gyrus of adult trained rats expressed less 5-HTR, while dentate gyrus of old increased them. Basomedial amygdaloid nucleus in old trained rats expressed more 5-HTR; while in the basolateral amygdaloid nucleus they were augmented in both groups. Training decreased or did not change 5-HTR in caudate-putamen of adult or old animals. The above profile of 5-HTR expression is consistent with previous reports, and suggests that memory formation and aging modulates 5-HTR expression in brain areas relevant to memory systems.
Behavioural Brain Research 07/2004; 152(2):425-436. · 3.39 Impact Factor