The 5-HTlA receptor agonist flesinoxan increases aversion in a model of panic-like anxiety in rats

Jenck, F.; Martin, James R.; Moreau, Jean‐Luc

doi:10.1177/026988119901300209

Cited by 16 publications

(3 citation statements)

References 33 publications

(52 reference statements)

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“…Secondly, the study was carried out with only one dose of the drug, and it could be useful to explore both lower and higher doses since a previous study has reported that flesinoxan induced a dose-dependent PRL response (Pitchot et al 1995). Moreover, a recent report has demonstrated a dose-dependent decrease in threshold for acute fear responses recorded in rats following administration of flesinoxan (Jenck et al 1999). Thirdly, the lack of a placebo-controlled flesinoxan also limits the conclusions of this study.…”

Section: Discussionmentioning

confidence: 99%

5-HT1A dysfunction in borderline personality disorder

et al. 2002

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The results show major involvement of serotonergic function in BPD and are consistent with previous studies linking lower serotonergic activity with impulsivity. More particularly, our data suggest that BPD is characterized by lower 5-HT1A receptor sensitivity. Moreover, the data support the involvement of 5-HT1A activity in suicidal behaviour. However, this conclusion is limited because other hormonal responses such as ACTH and cortisol were not assessed, and because BPD was assessed by a self-report questionnaire and not a structured clinical interview.

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Section: Discussionmentioning

confidence: 99%

5-HT1A dysfunction in borderline personality disorder

et al. 2002

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“…lever pressing) which allow them to interrupt the stimulation and escape from it [89]. Drugs known to acutely ameliorate (alprazolam, clonazepam) or precipitate (yohimbine, caffeine,¯esinoxan) panic attacks in patients were found to acutely and dose-dependently reduce or enhance, respectively, aversion induced by dPAG stimulation [59,61]. However, this model also revealed paradoxical drug effects.…”

Section: Panic Disorder (Pd)mentioning

confidence: 99%

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

Blanchard

Griebel

Blanchard

2001

Neuroscience &Amp; Biobehavioral Reviews

411

251

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The natural defensive behaviors of laboratory mice have been evaluated in both seminatural and highly structured situations; and characterized in terms of eliciting stimuli, response to pharmacological agents, behavior patterns, and outcome or effect on the social and physical environment. The defense patterns of laboratory mice and rats are generally similar, but mice show risk assessment on initial exposure to highly threatening stimuli while rats do not, while rats display alarm vocalizations, missing in mice. Quantitative differences in freezing and¯ight for laboratory mice and rats appear to largely re¯ect domestication effects, with wild mice and rats more similar to each other. This nexus of detailed within-species and comparative data on defense patterns makes it possible to reliably elicit speci®c defenses in mice or rats in an experimental context, providing well-validated assays of the natural defensive behaviors themselves, as opposed tò models' of defense.The mouse±rat comparisons indicate considerable cross-species generality for these defense patterns, as does a scattered but considerable literature on other mammalian species, generally involving ®eld studies and typically focusing on those aspects of defensive behavior that are visible at a distance, such as vigilance, or¯ight. Although potential homologies between normal mouse and human defense systems should ideally involve all four pattern components (stimulus, organismic factors, response characteristics, outcome), predictive validity in terms of response to drugs active against speci®c defensive psychopathology is the most extensively investigated of these. Flight, as measured in the Mouse Defense Test Battery shows a consistently appropriate response to panicolytic, panicogenic, and panic-neutral drugs, while some other predictive`panic models' (dPAG-stimulation; DMH-inhibition; possibly conditioned suppression of drinking paradigms) also elicit and (indirectly) measure behaviors potentially related to¯ight. Models unrelated to¯ight (e.g. ultrasonic vocalization to conditioned stimuli); or for which¯ight elements may a relatively minor contributor to the behavior measured (Elevated T-maze) are less predictive of panicolytic or panicogenic action. These ®ndings indicate that natural defensive behaviors provide a well-characterized pattern for analysis of effects of genetic or other physiological manipulations in the mouse, and may also serve as a model for analysis of defenserelated human psychopathology. q 2001 Elsevier Science Ltd. All rights reserved. The recent explosion of genetic techniques and genetically modi®ed animals has greatly exacerbated the need for comprehensive, natural, models or assays of behavior that are relevant to mice, the mammalian species of choice for genetic research [25]; and has additionally focused attention on issues of construction and validation of these tests.Minimally, a behavioral model/assay should enable the reliable elicitation and measurement of a qualitatively consistent behavior pattern for ...

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“…A relationship to panic states has also been claimed for potent actions of flesinoxan and other 5-HT 1A agonists in the USV procedure (Griebel 1995;Millan et al 1997;Sànchez and Mørk 1999), which were corroborated herein. However, the exacerbation of panic states by flesinoxan in man (Van Vliet et al 1996;Jenck et al 1999) questions this interpretation. …”

Section: Usv Testmentioning

confidence: 99%

Anxiolytic Properties of the Selective, Non-peptidergic CRF1 Antagonists, CP154,526 and DMP695 A Comparison to Other Classes of Anxiolytic Agent

Millan

2001

Neuropsychopharmacology

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The selective, non-peptidergic corticotropin-releasing factor (CRF) 1 receptor antagonists, CP154,526 and DMP695, dose-dependently increased punished responses of rats in a Vogel conflict test and enhanced social interaction (SI) of rats in an unfamiliarCorticotropin-releasing factor (CRF) plays a crucial role in modulation of the release of adrenocorticotrophic hormone from the anterior pituitary (De Souza 1995). In addition, CRF is broadly distributed throughout the mammalian central nervous system (CNS), being concentrated in corticolimbic regions such as amygdala, hippocampus, and periaqueductal gray (PAG) and frontal cortex (FCX), as well as the locus coeruleus (LC) and dorsal raphe nucleus (DRN), the origin of ascending adrenergic and serotonergic projections, respectively (Sawchenko et al. 1993;Van Bockstaele et al. 1996;Price et al. 1998;Steckler and Holsboer 1999). In line with this organization, independently of the hypothalamocorticotrophic axis, cerebral CRF-containing neurones fulfill an important role in the control of emotional behavior (Adamec and McKay 1993;De Souza 1995;Mitchell 1998;Steckler and Holsboer 1999;Smagin and Dunn 2000), actions expressed via two principal subtypes of CRF receptor, both of which positively couple to adenyl cyclase (Grigoriadis et al. 1996). CRF 1 receptors bind CRF and a related neuropeptide, urocortin, with high affinity whereas CRF 2 receptors display a NO . 4 distinct preference for the latter (Donaldson et al. 1996;Grigoriadis et al. 1996). Of several splice variants of the latter, the CRF 2 ␣ subtype is found predominantly in the rodent CNS, notably in several corticolimbic regions enriched in CRF itself, such as the hippocampus, medial amygdala, septum, olfactory bulb, and raphe nuclei, although species differences in this regard should be pointed out (Chalmers et al. 1995;Sánchez et al. 1999). Studies of mRNA encoding CRF 1 receptors and of the corresponding peptide have established a contrasting pattern of distribution in rats with a predominance of CRF 1 over CRF 2 ␣ sites in anterior pituitary, FCX and basolateral amygdala, as well as high levels in the hippocampus and PAG (Potter et al. 1994;Chalmers et al. 1995;Sánchez et al. 1999;Chen et al. 2000).These observations provide a neuroanatomical substrate for a potential role of CRF 1 and/or CRF 2 receptors in the control of mood (Coplan et al. 1996;Steckler and Holsboer 1999), and, in this regard, there is a diversity of evidence implicating CRF 1 sites in the modulation of anxious states. First, several studies have reported anxiogenic actions of CRF (and urocortin) upon i.c.v. administration (see Steckler and Holsboer, 1999) and similar effects have been seen upon direct introduction into the dorsal PAG (Martins et al. 1997), basolateral amygdala (Sajdyk et al. 1999), and hippocampus (Radulovic et al. 1999), structures possessing a high density of CRF 1 receptors. Second, direct evidence for participation of CRF 1 receptors in anxiogenic actions is derived from studies of antisense probes for their ...

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The 5-HTlA receptor agonist flesinoxan increases aversion in a model of panic-like anxiety in rats

Cited by 16 publications

References 33 publications

5-HT1A dysfunction in borderline personality disorder

5-HT1A dysfunction in borderline personality disorder

Mouse defensive behaviors: pharmacological and behavioral assays for anxiety and panic

Anxiolytic Properties of the Selective, Non-peptidergic CRF1 Antagonists, CP154,526 and DMP695 A Comparison to Other Classes of Anxiolytic Agent

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