Somatodendritic 5-HT1A receptors are critically involved in the anxiolytic effects of 8-OH-DPAT

Remy, S. Maurel; Schreiber, Rudy; Dalmus, M.; Vry, Jean De

doi:10.1007/bf02247397

Cited by 54 publications

(24 citation statements)

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“…The involvement of the red nucleus in locomotor function in the rat suggests that bradykinin might be involved in the regulation and control of motor function (Ruigrok et al, 1996, Wishaw et al, 1996. B2 staining was also observed in the raphe nucleus, suggesting a role in anxiolytic be- havior and antinociception (Lichtman et al, 1996;Remy et al, 1996), a common effect of bradykinin administration (Ribeiro and Silva, 1973;Pela et al, 1996). Staining was found in a number of other regions without any known function for bradykinin, including the hippocampus, basal forebrain, cerebellum ganglia, visual system, olfactory system, and cerebral cortex.…”

Section: Discussionmentioning

confidence: 93%

B2 bradykinin receptor immunoreactivity in rat brain

et al. 2000

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Bradykinin has long been known to exist in the central nervous system and has been hypothesized to mediate specific functions. Despite an increasing understanding of the functions of bradykinin, little is known about the cell types expressing the bradykinin receptor within the brain. The present investigation employed a monoclonal antibody directed against the 15-amino-acid portion of the C-terminal of the human bradykinin B2 receptor to establish the cellular distribution of bradykinin B2 receptor immunoreactivity in the rat brain. Bradykinin B2 receptor immunoreactivity was ubiquitously and selectively observed in neurons, including those within the olfactory bulb, cerebral cortex, hippocampus, basal forebrain, basal ganglia, thalamus, hypothalamus, cerebellum, and brainstem nuclei. Bradykinin B2 receptor immunoreactivity was also present in the circumventricular organs including choroid plexus, subfornical organ, median eminence, and area postrema. Double-labeling experiments colocalizing the bradykinin B2 receptor with the neuronal marker NeuN or the astrocytic marker glial fibrillary acidic protein revealed that virtually 100% of the bradykinin B2 receptor-immunoreactive positive cells were neurons. The widespread distribution of bradykinin B2 receptor immunoreactivity in neuronal compartments suggests a greater than previously appreciated role for this peptide in neuronal function.

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Section: Discussionmentioning

confidence: 93%

B2 bradykinin receptor immunoreactivity in rat brain

et al. 2000

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“…Systemic administration of 5-HT 1A receptor agonists such as buspirone and antagonists such as WAY 100635 produce inconsistent effects on anxiety-related behaviors in various rodent models of anxiety (14,(24)(25)(26)(27). This may relate to the existence of distinct 5-HT 1A receptor populations that produce opposing effects on anxiety regulation.…”

Section: Discussionmentioning

confidence: 99%

Elevated anxiety and antidepressant-like responses in serotonin 5-HT _1A receptor mutant mice

Heisler

Chu²,

Brennan³

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

635

389

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The brain serotonin (5-hydroxytryptamine; 5-HT) system is a powerful modulator of emotional processes and a target of medications used in the treatment of psychiatric disorders. To evaluate the contribution of serotonin 5-HT 1A receptors to the regulation of these processes, we have used gene-targeting technology to generate 5-HT 1A receptormutant mice. These animals lack functional 5-HT 1A receptors as indicated by receptor autoradiography and by resistance to the hypothermic effects of the 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT). Homozygous mutants display a consistent pattern of responses indicative of elevated anxiety levels in open-field, elevated-zero maze, and novel-object assays. Moreover, they exhibit antidepressant-like responses in a tail-suspension assay. These results indicate that the targeted disruption of the 5-HT 1A receptor gene leads to heritable perturbations in the serotonergic regulation of emotional state. 5-HT 1A receptor-null mutant mice have potential as a model for investigating mechanisms through which serotonergic systems modulate affective state and mediate the actions of psychiatric drugs. The brain serotonin (5-hydroxytryptamine; 5-HT) system has been strongly implicated in the neural regulation of mood and anxiety state. Accordingly, many commonly used antidepressant and antianxiety medications target this system (1). The complex physiological actions of serotonin are mediated by a heterogeneous family of at least 14 distinct receptor subtypes (2). Although the relative contributions of individual receptor subtypes to the serotonergic regulation of mood are incompletely understood, particular attention has focused on the 5-HT 1A receptor subtype. Partial agonists at this receptor, such as buspirone, are in clinical use as anxiolytics (3), and 5-HT 1A receptor antagonists are reported to accelerate the therapeutic effects of antidepressant medications (4).These compounds produce complex effects on brain function through interactions with functionally distinct populations of 5-HT 1A receptors. 5-HT 1A receptors located on serotonergic neuronal cell bodies and dendrites are the predominant somatodendritic autoreceptors of these neurons; their activation suppresses serotonergic neuronal activity (5, 6). In addition, postsynaptic 5-HT 1A receptors are expressed in numerous serotonergic projection sites such as the cerebral cortex, septal nuclei, hippocampus, and amygdala (7). The relatively selective 5-HT 1A receptor agonist 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) and antagonist WAY 100635 (8) have been used as pharmacological probes of 5-HT 1A receptor function. Systemic administration of 8-OH-DPAT produces hyperphagia, hypothermia, and an anxiolytic-like effect in rodents (9-12). The behavioral and physiological effects of 8-OH-DPAT are blocked by pretreatment with WAY 100635 (12-14).To complement pharmacological approaches to the study of 5-HT 1A receptor function, we have used a gene-targeting strategy to generate a line of m...

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“…The 5-HT 1A receptors are also very abundant in the amygdala. Thus, it cannot be excluded that postsynaptic 5-HT 1A receptors play a role in the mechanism of action of these compounds, but studies using local application of these compounds suggest that anxiolytic effects are mediated through the somatodendritic 5-HT 1A receptors in the dorsal raphe (Remy et al 1996).…”

Section: Discussionmentioning

confidence: 99%

The effects of A 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635

Bosker¹,

Vrinten²,

Klompmakers³

et al. 1997

Naunyn-Schmiedeberg's Arch Pharmacol

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The modulation of extracellular 5-hydroxytryptamine (5-HT) in the central nucleus of the amygdala (CeA) by 5-HT1A receptors was studied by intracerebral microdialysis in awake and freely moving rats. Local administration of 1 microM tetrodotoxin (TTX), 60 mM K+ and perfusion with Ca(2+)-free Ringer containing EGTA confirmed that the major part of dialysate 5-HT levels from the CeA is of neuronal origin. Administration of 300 nM of RU 24969, a 5-HT1B receptor agonist, through the probe into the CeA decreased dialysate 5-HT levels to 67.2% of the baseline value. Systemic administration of the 5-HT1A receptor agonists 8-OH-DPAT and flesinoxan dose-dependently decreased 5-HT levels in the CeA. The effect of 0.3 mg/kg of flesinoxan could be completely antagonized by systemic administration of 0.05 mg/kg WAY 100635, a 5-HT1A receptor antagonist. WAY 100635 alone had only minimal effects at this dose. These data show that a major part of the extracellular 5-HT in the CeA stems from 5-HT neurons and that the amount of 5-HT released into this brain region can be modulated by 5-HT1A receptors.

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Somatodendritic 5-HT1A receptors are critically involved in the anxiolytic effects of 8-OH-DPAT

Cited by 54 publications

References 5 publications

B2 bradykinin receptor immunoreactivity in rat brain

B2 bradykinin receptor immunoreactivity in rat brain

Elevated anxiety and antidepressant-like responses in serotonin 5-HT _1A receptor mutant mice

The effects of A 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635

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Somatodendritic 5-HT1A receptors are critically involved in the anxiolytic effects of 8-OH-DPAT

Cited by 54 publications

References 5 publications

B2 bradykinin receptor immunoreactivity in rat brain

B2 bradykinin receptor immunoreactivity in rat brain

Elevated anxiety and antidepressant-like responses in serotonin 5-HT 1A receptor mutant mice

The effects of A 5-HT1A receptor agonist and antagonist on the 5-hydroxytryptamine release in the central nucleus of the amygdala: a microdialysis study with flesinoxan and WAY 100635

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Elevated anxiety and antidepressant-like responses in serotonin 5-HT _1A receptor mutant mice