Increases in the activity of tryptophan hydroxylase from rat cortex and midbrain in response to acute or repeated sound stress are blocked by adrenalectomy and restored by dexamethasone treatment

Singh, Virendra; Corley, Karl C.; Phan, Tam-Hao; Boadle-Biber, Margaret C.

doi:10.1016/0006-8993(90)90898-l

Cited by 121 publications

(83 citation statements)

References 49 publications

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“…There is now, mainly electrophysiological, evidence showing that glucocorticoids may play a role in the regulation of serotonergic neurotransmission (Laaris et al, 1995). Adrenalectomy, however, exerts no major effects on the firing rate of 5-HT neurons (Laaris et al, 1995) and on tryptophan hydroxylase activity (Singh et al, 1990;Sze et al, 1976;Kizer et al, 1976) under basal conditions. Moreover, hippocampal extracellular levels of 5-HT and 5-HIAA are unchanged under resting (and CRH-stimulated) conditions in adrenalectomized rats (Linthorst et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Altered Serotonergic Neurotransmission but Normal Hypothalamic–Pituitary–Adrenocortical Axis Activity in Mice Chronically Treated with the Corticotropin-Releasing Hormone Receptor Type 1 Antagonist NBI 30775

Oshima

Flachskamm

Reul

et al. 2003

Neuropsychopharmacol

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Antagonists of the corticotropin-releasing hormone receptor type 1 (CRH-R1) are regarded as promising tools for the treatment of stress-related psychiatric disorders. Owing to the intricate relationship between CRH and serotonin (5-HT), we studied the effects of chronic oral treatment of C57Bl6/N mice with the CRH-R1 antagonist NBI 30775 (formerly known as R121919) on hippocampal serotonergic neurotransmission during basal (on 15th day of treatment) and stress (forced swimming; on 16th day of treatment) conditions by in vivo microdialysis. Given the important role of CRH in the regulation of hypothalamic-pituitary-adrenocortical (HPA) axis activity and behavior, the effects of NBI 30775 on dialysate-free corticosterone levels, and on home cage and forced swimmingrelated behavior were also assessed. Chronic administration of NBI 30775 (18.4 7 0.9 mg/kg/day) did not result in alterations in food consumption and body weight. NBI 30775 caused complex changes in hippocampal serotonergic neurotransmission. Whereas no effects on the diurnal rhythms of 5-HT and its metabolite 5-hydroxyindoleacetic acid were found, the responses of the neurotransmitter and its metabolite to 10 min of forced swim stress were reduced and prolonged, respectively. NBI 30775 did not change free corticosterone levels over the diurnal rhythm. Moreover, NBI 30775-treated mice showed a similar forced swim stress-induced increase in corticosterone as observed in the control group. No effects of NBI 30775 on home cage, and swim stress-related active behaviors (climbing, swimming) and immobility were found. Thus, whereas chronic antagonism of CRH-R1 did not compromise HPA axis performance and behavior, distinct changes in serotonergic neurotransmission developed. Owing to the important role of 5-HT in the pathophysiology of mood and anxiety disorders, the latter observation may contribute to the therapeutical efficacy of CRH-R1 antagonists in these illnesses.

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Section: Discussionmentioning

confidence: 99%

Altered Serotonergic Neurotransmission but Normal Hypothalamic–Pituitary–Adrenocortical Axis Activity in Mice Chronically Treated with the Corticotropin-Releasing Hormone Receptor Type 1 Antagonist NBI 30775

Oshima

Flachskamm

Reul

et al. 2003

Neuropsychopharmacol

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“…Acute stress increases Tph (presumably Tph2 isoform) activity in the DR [140] and a stress-induced rise in activity due to phosphorylation of the enzyme has been observed [141]. Inescapable randomly presented sound stress resulted in a transient phosphorylationdependent rise in enzymatic activity of Tph in the MnR nucleus, whereas chronic sound stress has been shown to induce sustained and phosphatase-resistant increases in Tph activity, providing initial evidence that increases in Tph activity following chronic stress are mediated by increased Tph expression [142].…”

Section: Tph2 Hypothalamic -Pituitary-adrenal System and Environmentmentioning

confidence: 99%

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour

Lesch

Araragi

Waider

et al. 2012

Phil. Trans. R. Soc. B

131

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Aggression, which comprises multi-faceted traits ranging from negative emotionality to antisocial behaviour, is influenced by an interaction of biological, psychological and social variables. Failure in social adjustment, aggressiveness and violence represent the most detrimental long-term outcome of neurodevelopmental disorders. With the exception of brain-specific tryptophan hydroxylase-2 (Tph2), which generates serotonin (5-HT) in raphe neurons, the contribution of gene variation to aggression-related behaviour in genetically modified mouse models has been previously appraised (Lesch 2005 Novartis Found Symp. 268, 111 -140; Lesch & Merschdorf 2000 Behav. Sci. Law 18, 581 -604). Genetic inactivation of Tph2 function in mice led to the identification of phenotypic changes, ranging from growth retardation and late-onset obesity, to enhanced conditioned fear response, increased aggression and depression-like behaviour. This spectrum of consequences, which are amplified by stress-related epigenetic interactions, are attributable to deficient brain 5-HT synthesis during development and adulthood. Human data relating altered TPH2 function to personality traits of negative emotionality and neurodevelopmental disorders characterized by deficits in cognitive control and emotion regulation are based on genetic association and are therefore not as robust as the experimental mouse results. Mouse models in conjunction with approaches focusing on TPH2 variants in humans provide unexpected views of 5-HT's role in brain development and in disorders related to negative emotionality, aggression and antisocial behaviour.Keywords: tryptophan hydroxylase (TPH2); cognition; emotion; impulsivity; aggression; violence INTRODUCTIONNegative emotionality, aggression and antisociality are complex temperamental traits and social behaviours that arise out of multiple causes involving biological and psychological dynamisms and social forces, and different forms of emotional behaviour may each result from different biopsychosocial pathways. The societal implications of aggressiveness, which results in numerous facets of aggressive behaviour and ranges from the establishment of hierarchies and dominance to antisocial behaviour and delinquency, have been examined with preclinical and clinical frameworks.Developmentally inappropriate conduct, aggressiveness and failure in social adjustment represent the most detrimental and harmful long-term outcome of a wide spectrum of neurodevelopmental disorders characterized by deficits in cognitive control and emotion regulation.In both humans and animals, the term aggression comprises a variety of behaviours that are heterogeneous for clinical phenomenology and neurobiological features. While the impact of complex cultural variables on behaviour impedes simple extrapolation of animal phenotypes to human traits, clinical observation, experimental paradigms in the laboratory and cluster/ factor-analytic statistics have been used in attempts to subdivide aggression. On the basis of different approaches, hu...

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“…Regarding tryptophan hydroxylase, there is evidence for a key regulatory, albeit permissive, role of corticoids (Chaouloff 1993). Thus, sound stress increases tryptophan hydroxylase activity through glucocorticoid receptors, an effect prevented by adrenalectomy (Singh et al 1990). On the other hand, adrenalectomy does not affect footshock-induced rises in 5-HT synthesis/metabolism (Dunn 1988), thereby suggesting again some specificity with regard to the nature of the stimulus.…”

Section: -Ht Synthesis/metabolism and Stressmentioning

confidence: 99%

Serotonin and Stress

Chaouloff

Berton

Mormède

1999

Neuropsychopharmacology

223

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Forty-five years after its discovery, brain serotonin (5-HTSince the discovery of serotonin (5-hydroxytryptamine, 5-HT) in the mammalian brain (Twarog and Page 1953), the effects of stress upon serotonergic systems have been the focus of permanent research (Anisman and Zacharko 1982;Chaouloff 1993;Rueter et al. 1997). An overview of such research provides a reliable illustration of the progress made in that field. Early studies from the 1960s focused on the effects of stressors on brain 5-HT levels and synthesis. In the 1970s, drugs rendering possible the estimation of 5-HT turnover allowed a more detailed analysis of time-and region-dependent changes in serotonergic systems of stressed animals; in addition, reports regarding the influence of stressors upon the supply of tryptophan to the brain were first published during that period. In the 1980s, the recognition of the first subtypes of 5-HT receptors led to studies aimed at measuring the impact of acute and repeated stressors on these targets; in parallel, key studies appeared that were devoted to (1) the roles of stress hormones (e.g., corticoids) in the control of central serotonergic activity, and (2) the effects of stressors on 5-HT nerve firing. Currently, numerous studies explore the effects of stressors on extracellular 5-HT levels (as assessed by the microdialysis technique) and 5-HT receptor-coupled second messengers.An overview of 30 years of research on stress and 5-HT indeed favors the hypothesis that numerous components of central serotonergic systems are sensitive to stressors. This result would thus fit, at first glance, with therapeutic data in anxious and/or depressed patients, data suggesting that 5-HT is an important component of the central network that provides adaptation to stress. However, among the questions that remain regarding the role of 5-HT in this network, one is of particular importance: is 5-HT a fine modulator or an onor-off switch? If the former proposal is correct, one would expect, among other criteria, that 5-HT responds specifically to certain stressors, both in terms of duraFrom the NeuroGénétique et Stress,

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Increases in the activity of tryptophan hydroxylase from rat cortex and midbrain in response to acute or repeated sound stress are blocked by adrenalectomy and restored by dexamethasone treatment

Cited by 121 publications

References 49 publications

Altered Serotonergic Neurotransmission but Normal Hypothalamic–Pituitary–Adrenocortical Axis Activity in Mice Chronically Treated with the Corticotropin-Releasing Hormone Receptor Type 1 Antagonist NBI 30775

Altered Serotonergic Neurotransmission but Normal Hypothalamic–Pituitary–Adrenocortical Axis Activity in Mice Chronically Treated with the Corticotropin-Releasing Hormone Receptor Type 1 Antagonist NBI 30775

Targeting brain serotonin synthesis: insights into neurodevelopmental disorders with long-term outcomes related to negative emotionality, aggression and antisocial behaviour

Serotonin and Stress

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