P. Pechtel, Laura Murray, Laura E. Brumariu, K. Lyons-Ruth
Despite important progress in understanding the complex caregiving system, developmental research has only recently begun to focus on the mother's internal affective state and its role in sensitive caregiving behavior. This review will summarize recent findings of functional neuroimaging research to elaborate on the neural components associated with maternal sensitive care or disrupted responsiveness to infant communications. First, maternal emotion reactivity and regulation, as well as maternal reward responsiveness to infant cues, will be reviewed among healthy mothers. Then, emotion and reward-related processes among mothers who display sensitive versus disrupted caregiving will be explored. Finally, these patterns of response will be compared to patterns of response among mothers with psychiatric disorders, including depression, posttraumatic stress disorder, and substance abuse. The aim of this review is to examine whether differences in emotion reactivity and regulation, as well as in the encoding of infant stimuli as rewarding, are related either to maternal psychopathology or to maternal difficulties in responding promptly and appropriately to their infants. A summary of the challenges facing developmental neuroscience research in furthering our understanding of maternal responses to infants will close this review.
{"title":"Reactivity, regulation, and reward responses to infant cues among mothers with and without psychopathology: an fMRI review","authors":"P. Pechtel, Laura Murray, Laura E. Brumariu, K. Lyons-Ruth","doi":"10.3402/tdp.v1i0.19673","DOIUrl":"https://doi.org/10.3402/tdp.v1i0.19673","url":null,"abstract":"Despite important progress in understanding the complex caregiving system, developmental research has only recently begun to focus on the mother's internal affective state and its role in sensitive caregiving behavior. This review will summarize recent findings of functional neuroimaging research to elaborate on the neural components associated with maternal sensitive care or disrupted responsiveness to infant communications. First, maternal emotion reactivity and regulation, as well as maternal reward responsiveness to infant cues, will be reviewed among healthy mothers. Then, emotion and reward-related processes among mothers who display sensitive versus disrupted caregiving will be explored. Finally, these patterns of response will be compared to patterns of response among mothers with psychiatric disorders, including depression, posttraumatic stress disorder, and substance abuse. The aim of this review is to examine whether differences in emotion reactivity and regulation, as well as in the encoding of infant stimuli as rewarding, are related either to maternal psychopathology or to maternal difficulties in responding promptly and appropriately to their infants. A summary of the challenges facing developmental neuroscience research in furthering our understanding of maternal responses to infants will close this review.","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/tdp.v1i0.19673","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69949970","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Translational research from a developmental viewpoint – Embarking on a neuroscientific journey","authors":"F. Zepf","doi":"10.3402/tdp.v1i0.21623","DOIUrl":"https://doi.org/10.3402/tdp.v1i0.21623","url":null,"abstract":"","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69950145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Purpose of the study Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. We have developed a human model of reward processing to investigate the neural correlates of anhedonia. Methods We report the data from studies that examined reward processing using functional magnetic resonance imaging (fMRI) in those vulnerable to depression. We also report the effects of antidepressant medications on our neural model of reward processing and on the resting state in healthy volunteers. Results Our results thus far indicate that deficits in reward processing are apparent in those vulnerable to depression, and also that antidepressant medication modulates reward processing and resting state functional connectivity in parts of the brain consistent with serotonin and catecholamine transmitter pathways in healthy volunteers. Conclusions We conclude that this type of human model of reward processing might be useful in detecting biomarkers for depression and also in illuminating why antidepressant medications may not be very effective in treating anhedonia.
{"title":"Reward, Rest, and Antidepressant Drug Action","authors":"C. McCabe","doi":"10.3402/TDP.V1I0.18652","DOIUrl":"https://doi.org/10.3402/TDP.V1I0.18652","url":null,"abstract":"Purpose of the study Reduced subjective experience of reward (anhedonia) is a key symptom of major depression. We have developed a human model of reward processing to investigate the neural correlates of anhedonia. Methods We report the data from studies that examined reward processing using functional magnetic resonance imaging (fMRI) in those vulnerable to depression. We also report the effects of antidepressant medications on our neural model of reward processing and on the resting state in healthy volunteers. Results Our results thus far indicate that deficits in reward processing are apparent in those vulnerable to depression, and also that antidepressant medication modulates reward processing and resting state functional connectivity in parts of the brain consistent with serotonin and catecholamine transmitter pathways in healthy volunteers. Conclusions We conclude that this type of human model of reward processing might be useful in detecting biomarkers for depression and also in illuminating why antidepressant medications may not be very effective in treating anhedonia.","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/TDP.V1I0.18652","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69949826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Alterations in serotonergic (5-HT) neurotransmission are thought to play a decisive role in affective disorders and impulse control. However, the studies on the involvement of cerebral 5-HT availability and its effects on behavioral inhibition in healthy subjects yielded inconsistent findings. It appears that central nervous serotonergic neurotransmission is rather related to context-specific aspects of suppression of behavior than motor response inhibition alone. Crockett et al. aimed to disentangle the involvement of 5-HT on aspects of motor response inhibition, punishment-induced suppression of inappropriate responses, and sensitivity toward aversive outcomes in a single behavioral Go-NoGo task using a fixed dosage acute tryptophan depletion (ATD) procedure. While motor response inhibition was unaffected, punishmentinduced inhibition was reported to be abolished by ATD. Objective A recently developed refined and body-weight-adjusted ATD protocol (Moja-De) was applied. We aimed to replicate the experiment of Crockett et al. using a Go-NoGo task in a comparable sample of young healthy adults. Methods Central nervous 5-HT synthesis was lowered by administering a body-weight-adapted ATD procedure in a randomized, double-blind, within-subject, repeated measures design in 24 healthy volunteers. A tryptophan-balanced amino acid beverage served as a control condition. The above-mentioned Go-NoGo task was administered 180 minutes after beverage intake. Blood samples were obtained at four time points: baseline, 90 minutes, 180 minutes, and 270 minutes after beverage administration. Results ATD produced significant depletion of plasma levels of both total and free tryptophan at all post-ATD time points, compared with a balanced amino acid load (BAL). While overall Go-NoGo performance accuracy was not affected by ATD, response times significantly decreased. Also, the ability to adjust behavioral responding in regard to aversive outcome magnitude and behavioral adjustments following error contingent punishment remain intact after decreased brain 5-HT synthesis. However, no dissociation effect of ATD on punishment-induced inhibition was observed. Conclusion Our study using a recently developed refined and individually adjusted tryptophan depletion procedure assessed with the identical behavioral task as used by Crockett et al. yielded challenging results compared with the original study in terms of the role of 5-HT in behavioral inhibition. Our findings suggest that ATD Moja-De facilitates adequate responding (improved response times) at equally low performance accuracy, compared with BAL. ATD-specific reductions in punishment-induced inhibition were not observed in the present sample, thus challenging the suggested role of 5-HT related to the aversive context of inhibitory behavior in the original study. Overall, our results suggest that body weight adjusted Moja-De trypthophan depletion does not result in disruptions of punishment related behav
{"title":"Effects of Acute Tryptophan Depletion Moja-De on Behavioral Inhibition in Healthy Adults","authors":"T. J. Gaber","doi":"10.3402/tdp.v1i0.18676","DOIUrl":"https://doi.org/10.3402/tdp.v1i0.18676","url":null,"abstract":"Background Alterations in serotonergic (5-HT) neurotransmission are thought to play a decisive role in affective disorders and impulse control. However, the studies on the involvement of cerebral 5-HT availability and its effects on behavioral inhibition in healthy subjects yielded inconsistent findings. It appears that central nervous serotonergic neurotransmission is rather related to context-specific aspects of suppression of behavior than motor response inhibition alone. Crockett et al. aimed to disentangle the involvement of 5-HT on aspects of motor response inhibition, punishment-induced suppression of inappropriate responses, and sensitivity toward aversive outcomes in a single behavioral Go-NoGo task using a fixed dosage acute tryptophan depletion (ATD) procedure. While motor response inhibition was unaffected, punishmentinduced inhibition was reported to be abolished by ATD. Objective A recently developed refined and body-weight-adjusted ATD protocol (Moja-De) was applied. We aimed to replicate the experiment of Crockett et al. using a Go-NoGo task in a comparable sample of young healthy adults. Methods Central nervous 5-HT synthesis was lowered by administering a body-weight-adapted ATD procedure in a randomized, double-blind, within-subject, repeated measures design in 24 healthy volunteers. A tryptophan-balanced amino acid beverage served as a control condition. The above-mentioned Go-NoGo task was administered 180 minutes after beverage intake. Blood samples were obtained at four time points: baseline, 90 minutes, 180 minutes, and 270 minutes after beverage administration. Results ATD produced significant depletion of plasma levels of both total and free tryptophan at all post-ATD time points, compared with a balanced amino acid load (BAL). While overall Go-NoGo performance accuracy was not affected by ATD, response times significantly decreased. Also, the ability to adjust behavioral responding in regard to aversive outcome magnitude and behavioral adjustments following error contingent punishment remain intact after decreased brain 5-HT synthesis. However, no dissociation effect of ATD on punishment-induced inhibition was observed. Conclusion Our study using a recently developed refined and individually adjusted tryptophan depletion procedure assessed with the identical behavioral task as used by Crockett et al. yielded challenging results compared with the original study in terms of the role of 5-HT in behavioral inhibition. Our findings suggest that ATD Moja-De facilitates adequate responding (improved response times) at equally low performance accuracy, compared with BAL. ATD-specific reductions in punishment-induced inhibition were not observed in the present sample, thus challenging the suggested role of 5-HT related to the aversive context of inhibitory behavior in the original study. Overall, our results suggest that body weight adjusted Moja-De trypthophan depletion does not result in disruptions of punishment related behav","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/tdp.v1i0.18676","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69950143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Decades of research have linked serotonin (5-HT) to prosocial behavior across species; however, the specific mechanisms mediating this relationship have not yet been elucidated. We examine the influence of 5-HT on prosocial behavior by considering its function in basic motivational processes. Influential theories have implicated 5-HT in impulsivity, aversive processing, and behavioral inhibition. Design In a series of behavioral experiments performed in humans, we showed that 5-HT is critical for behavioral inhibition in the face of aversive predictions, but not overall motor response inhibition or sensitivity to aversive outcomes. We further investigated how 5-HT shapes prosocial behavior by examining its influence on costly punishment, the willingness to incur personal costs to punish social norm violations. Several studies have shown that costly punishment of cheaters promotes group cooperation, suggesting that costly punishment is a prosocial act. However, costly punishment can be driven by prosocial fairness concerns, or by antisocial retributive motives. Results 5-HT manipulations had bi-directional effects on costly punishment behavior; enhancing 5-HT function with citalopram reduced costly punishment, whereas depleting the 5-HT precursor tryptophan enhanced costly punishment. Neural and behavioral evidence suggested that 5-HT shapes punishment behavior by regulating retributive motives. Conclusion For our understanding of 5-HT in healthy and disordered cognitive and affective processing the implications of these findings are discussed.
{"title":"Serotonin and Aversive Processing in Social and Nonsocial Contexts","authors":"M. Crockett","doi":"10.3402/tdp.v1i0.18679","DOIUrl":"https://doi.org/10.3402/tdp.v1i0.18679","url":null,"abstract":"Background Decades of research have linked serotonin (5-HT) to prosocial behavior across species; however, the specific mechanisms mediating this relationship have not yet been elucidated. We examine the influence of 5-HT on prosocial behavior by considering its function in basic motivational processes. Influential theories have implicated 5-HT in impulsivity, aversive processing, and behavioral inhibition. Design In a series of behavioral experiments performed in humans, we showed that 5-HT is critical for behavioral inhibition in the face of aversive predictions, but not overall motor response inhibition or sensitivity to aversive outcomes. We further investigated how 5-HT shapes prosocial behavior by examining its influence on costly punishment, the willingness to incur personal costs to punish social norm violations. Several studies have shown that costly punishment of cheaters promotes group cooperation, suggesting that costly punishment is a prosocial act. However, costly punishment can be driven by prosocial fairness concerns, or by antisocial retributive motives. Results 5-HT manipulations had bi-directional effects on costly punishment behavior; enhancing 5-HT function with citalopram reduced costly punishment, whereas depleting the 5-HT precursor tryptophan enhanced costly punishment. Neural and behavioral evidence suggested that 5-HT shapes punishment behavior by regulating retributive motives. Conclusion For our understanding of 5-HT in healthy and disordered cognitive and affective processing the implications of these findings are discussed.","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/tdp.v1i0.18679","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69950232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Adolescents are impulsive and novelty seeking, normal behaviors that engage the adolescents in the world outside the home but also increase involvement in risky behaviors. Immaturity of frontal cortex circuits involved in executive function may be the main reason for this behavioral profile. As serotonergic innervation of the frontal cortex is critical for behavioral inhibition, we investigated the hypothesis that immaturity in serotonergically-mediated behavioral inhibition contributes to the adolescent behavioral profile. Design: To investigate the role of serotonergic innervation, we evaluated the behavioral and neurochemical effects of fluoxetine in adolescent (PN 28) and adult male rats (PN 70). Rats were treated with fluoxetine (0, 10 mg/kg) and tested in the light/dark anxiety test. In addition, the ability of fluoxetine (0, 2.5, 5 and 10 mg/kg at hourly intervals) to increase extracellular serotonin in the prefrontal cortex was measured using microdialysis. Finally, the ability of fluoxetine (10 mg/kg) to activate the immediate early gene c-fos relative to vehicle control was determined to investigate downstream effects of the increase in extracellular serotonin. Results: Fluoxetine did not inhibit behavior in the light/dark anxiety test in adolescents relative to vehicle control, but it did so in adults. However, the neurochemical effects of fluoxetine were comparable in adolescents and adults: fluoxetine elicited comparable increases in extracellular 5-HT in adolescents and adults. To examine the contribution of postsynaptic mechanisms, we evaluated the behavioral effects of the 5 HT1a agonist 8-OHDPAT and the 5 HT2 agonist mCPP. mCPP (0.5 or 1 mg/kg) produced comparable behavioral inhibition relative to vehicle control in adolescents and adults, but 8-OHDPAT (0.25, 0.5 mg/kg) did not. To determine if neural circuit activation by postsynaptic mechanisms was functional in adolescents, we tested the ability of fluoxetine (10 mg/kg) and 8-OHDPAT (0.5 mg/kg) to activate C-fos. Neither drug activated C-fos in amygdala or PVN of the hypothalamus. Conclusions: These results suggest that cortical inhibition of stress circuitry is immature in adolescents.
{"title":"Serotonin in Adolescence: Role in Behavioral Inhibition","authors":"C. Kuhn","doi":"10.3402/tdp.v1i0.18845","DOIUrl":"https://doi.org/10.3402/tdp.v1i0.18845","url":null,"abstract":"Background: Adolescents are impulsive and novelty seeking, normal behaviors that engage the adolescents in the world outside the home but also increase involvement in risky behaviors. Immaturity of frontal cortex circuits involved in executive function may be the main reason for this behavioral profile. As serotonergic innervation of the frontal cortex is critical for behavioral inhibition, we investigated the hypothesis that immaturity in serotonergically-mediated behavioral inhibition contributes to the adolescent behavioral profile. Design: To investigate the role of serotonergic innervation, we evaluated the behavioral and neurochemical effects of fluoxetine in adolescent (PN 28) and adult male rats (PN 70). Rats were treated with fluoxetine (0, 10 mg/kg) and tested in the light/dark anxiety test. In addition, the ability of fluoxetine (0, 2.5, 5 and 10 mg/kg at hourly intervals) to increase extracellular serotonin in the prefrontal cortex was measured using microdialysis. Finally, the ability of fluoxetine (10 mg/kg) to activate the immediate early gene c-fos relative to vehicle control was determined to investigate downstream effects of the increase in extracellular serotonin. Results: Fluoxetine did not inhibit behavior in the light/dark anxiety test in adolescents relative to vehicle control, but it did so in adults. However, the neurochemical effects of fluoxetine were comparable in adolescents and adults: fluoxetine elicited comparable increases in extracellular 5-HT in adolescents and adults. To examine the contribution of postsynaptic mechanisms, we evaluated the behavioral effects of the 5 HT1a agonist 8-OHDPAT and the 5 HT2 agonist mCPP. mCPP (0.5 or 1 mg/kg) produced comparable behavioral inhibition relative to vehicle control in adolescents and adults, but 8-OHDPAT (0.25, 0.5 mg/kg) did not. To determine if neural circuit activation by postsynaptic mechanisms was functional in adolescents, we tested the ability of fluoxetine (10 mg/kg) and 8-OHDPAT (0.5 mg/kg) to activate C-fos. Neither drug activated C-fos in amygdala or PVN of the hypothalamus. Conclusions: These results suggest that cortical inhibition of stress circuitry is immature in adolescents.","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"29 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/tdp.v1i0.18845","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69950301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT) synthesis. Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood–brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols, possibly because of an administration in accordance with the body weight of the subjects. It has been used in the preliminary clinical studies, but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. Design We tested ATD Moja-De (TRP-) in two strains of mice, C57BL/6 and BALB/cJ, which are reported to have impaired 5-HT synthesis relative to other strains of mice. Results ATD Moja-De lowered brain TRP, significantly decreased central nervous 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5 HIAA in both strains of mice, however, more so in C57 BL/6 than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A tryptophan-balanced control mixture did not increase 5-HT or 5-HIAA. Conclusion The present findings suggest that ATD Moja-De effectively suppresses central serotonergic function, and that the effects of ATD Moja-De are specific to serotonin function.
{"title":"Effects of Acute Tryptophan Depletion on Brain Serotonin Function and Concentrations of Dopamine and Norepinephrine in C57BL/6J and BALB/cJ Mice","authors":"C. Biskup","doi":"10.3402/TDP.V1I0.18747","DOIUrl":"https://doi.org/10.3402/TDP.V1I0.18747","url":null,"abstract":"Background Acute tryptophan depletion (ATD) is a method of lowering brain serotonin (5-HT) synthesis. Administration of large neutral amino acids (LNAA) limits the transport of endogenous tryptophan (TRP) across the blood–brain barrier by competition with other LNAAs and subsequently decreases serotonergic neurotransmission. A recent discussion on the specificity and efficacy of the ATD paradigm for inhibition of central nervous 5-HT has arisen. ATD Moja-De is a revised mixture of AAs which is less nauseating than conventional protocols, possibly because of an administration in accordance with the body weight of the subjects. It has been used in the preliminary clinical studies, but its effects on central 5-HT mechanisms and other neurotransmitter systems have not been validated in an animal model. Design We tested ATD Moja-De (TRP-) in two strains of mice, C57BL/6 and BALB/cJ, which are reported to have impaired 5-HT synthesis relative to other strains of mice. Results ATD Moja-De lowered brain TRP, significantly decreased central nervous 5-HT synthesis as indexed by 5-HTP levels after decarboxlyase inhibition, and lowered 5-HT and 5 HIAA in both strains of mice, however, more so in C57 BL/6 than in BALB/cJ. Dopamine and its metabolites as well as norepinephrine were not affected. A tryptophan-balanced control mixture did not increase 5-HT or 5-HIAA. Conclusion The present findings suggest that ATD Moja-De effectively suppresses central serotonergic function, and that the effects of ATD Moja-De are specific to serotonin function.","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3402/TDP.V1I0.18747","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69950281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Video presentation of the entire lecture can be accessed here . Objective : The method of acute tryptophan depletion (ATD) currently represents the most extensively applied challenge test to investigate the implication of the serotonin (5-HT) system in cognitive functions and psychiatric disorders. ATD consists of manipulating the availability of the essential amino acid tryptophan (TRP), the dietary 5-HT precursor, through administration of a TRP-free diet, which leads to a decreased availability of TRP in the brain and its synthesis into 5-HT. It is, therefore, assumed that a decrease in 5-HT release and subsequent blunted neurotransmission is the underlying mechanism for the behavioral effects of ATD. Methods : This paper reviews the behavioral effects of ATD and whether they can be directly related to a serotonergic dysfunction in the brain. Results : Direct evidence that ATD decreases extracellular 5-HT concentrations is, however, lacking, and several studies support the contribution of alternative mechanisms such as decreased nitric oxide synthase activity and cerebrovascular abnormalities that might underlie the behavioral effects of ATD. This may question the utility of the method as a selective serotonergic challenge tool. Conclusion : As the ATD method seems important in the investigation of 5-HT-related functions and dysfunctions, the potential of such alternative mechanisms and possible confounding factors should be taken into account for an adequate interpretation of data resulting from application of the method of ATD in both clinical and preclinical settings. (Published: 9 September 2013) Citation: Translational Developmental Psychiatry 2013, 1 : 18658 - http://dx.doi.org/10.3402/tdp.v1i0.18658
{"title":"Challenging the Serotonin System: A Mechanistic Approach to the Method of Acute Tryptophan Depletion in Rodents","authors":"Eva L. van Donkelaar","doi":"10.3402/tdp.v1i0.18658","DOIUrl":"https://doi.org/10.3402/tdp.v1i0.18658","url":null,"abstract":"Video presentation of the entire lecture can be accessed here . Objective : The method of acute tryptophan depletion (ATD) currently represents the most extensively applied challenge test to investigate the implication of the serotonin (5-HT) system in cognitive functions and psychiatric disorders. ATD consists of manipulating the availability of the essential amino acid tryptophan (TRP), the dietary 5-HT precursor, through administration of a TRP-free diet, which leads to a decreased availability of TRP in the brain and its synthesis into 5-HT. It is, therefore, assumed that a decrease in 5-HT release and subsequent blunted neurotransmission is the underlying mechanism for the behavioral effects of ATD. Methods : This paper reviews the behavioral effects of ATD and whether they can be directly related to a serotonergic dysfunction in the brain. Results : Direct evidence that ATD decreases extracellular 5-HT concentrations is, however, lacking, and several studies support the contribution of alternative mechanisms such as decreased nitric oxide synthase activity and cerebrovascular abnormalities that might underlie the behavioral effects of ATD. This may question the utility of the method as a selective serotonergic challenge tool. Conclusion : As the ATD method seems important in the investigation of 5-HT-related functions and dysfunctions, the potential of such alternative mechanisms and possible confounding factors should be taken into account for an adequate interpretation of data resulting from application of the method of ATD in both clinical and preclinical settings. (Published: 9 September 2013) Citation: Translational Developmental Psychiatry 2013, 1 : 18658 - http://dx.doi.org/10.3402/tdp.v1i0.18658","PeriodicalId":90753,"journal":{"name":"Translational developmental psychiatry","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2013-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69949882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：