Acute escitalopram but not contextual conditioning exerts a stronger “anxiogenic” effect in rats with high baseline “anxiety” in the acoustic startle paradigm

Pettersson, Robert; Näslund, Jakob; Nilsson, Staffan; Eriksson, Elias; Hagsäter, Sven Melker

doi:10.1007/s00213-014-3783-z

Cited by 9 publications

(8 citation statements)

References 42 publications

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“…Our observation that noise bursts, a stimulus more frequently used to elicit startle behaviour, elicit a moderate degree of freezing is in line with previous studies (22,32,33). We suggest this response, which displayed a considerable degree of test-retest inter-individual variation, to be a feasible paradigm for future investigations of the modulation of mild fear responses.…”

Section: Discussionsupporting

confidence: 93%

Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing

Hagsäter

Thorén

Pettersson

et al. 2018

Acta Neuropsychiatr.

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ObjectiveWhereas long-term administration of selective serotonin reuptake inhibitors (SSRIs) is effective for the treatment of anxiety disorders, acute administration of these drugs may exert a paradoxical anxiogenic effect. The aim of the present study was to explore the possible effect of an SSRI in situations of unconditioned or limited conditioned fear.MethodsMale Sprague Dawley rats were administered a single dose of an SSRI, escitalopram, before acquisition or expression of context conditioned fear, where noise bursts were used as the unconditioned stimulus. Freezing was assessed as a measure of unconditioned fear (=the acute response to noise bursts) or conditioned fear (=the response to the context), respectively.ResultsNoise bursts elicited an acute increase in freezing but no robust conditioned response 7 days after exposure. Administration of escitalopram before testing exacerbated the freezing response during presentation of the unconditioned stimulus and also unmasked a conditioned response; in contrast, administration of escitalopram prior to acquisition did not influence the conditioned response.ConclusionThe data suggest that freezing in rats exposed to a stimulus inducing relatively mild fear may be enhanced by acute pretreatment with an SSRI regardless of whether the freezing displayed by the animals is an acute unconditioned response to the stimulus in question or a conditioned response to the same stimulus.

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Section: Discussionsupporting

confidence: 93%

Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing

Hagsäter

Thorén

Pettersson

et al. 2018

Acta Neuropsychiatr.

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“…The observed MXE‐induced antidepressant‐like effect is not due to alterations in locomotor activity because the same dose of MXE did not enhance locomotor activity. Notably, we showed that a single injection of MXE induces anxiogenic and antidepressant effects, a pharmacological feature that this drug shares with ketamine (da Silva et al, ) and several selective 5‐HT reuptake inhibitors (SSRIs) (Griebel et al, ; Kurt et al, ; Pettersson et al, ). As such, we cannot exclude the possibility that, as reported for SSRIs and other agents that augment 5‐HT signalling, high doses of MXE may elicit an anxiety‐like state during the first few days (or weeks) of use, before anxiolytic effects emerge (Ravinder et al, ; Jonassen et al, ).…”

Section: Discussionmentioning

confidence: 99%

Methoxetamine affects brain processing involved in emotional response in rats

Zanda

Fadda

Antinori

et al. 2017

British J Pharmacology

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BACKGROUND AND PURPOSEMethoxetamine (MXE) is a novel psychoactive substance that is emerging on the Internet and induces dissociative effects and acute toxicity. Its pharmacological effects have not yet been adequately investigated. EXPERIMENTAL APPROACHWe examined a range of behavioural effects induced by acute administration of MXE (0.5-5 mg·kg À1 ; i.p.) in rats and whether it causes rapid neuroadaptive molecular changes. KEY RESULTS MXE (0.5-5 mg·kgÀ1 ) affected motor activity in a dose-and time-dependent manner, inducing hypermotility and hypomotility at low and high doses respectively. At low and intermediate doses (0.5 and 1 mg·kg À1 ), MXE induced anxious and/or obsessive-compulsive traits (marble burying test), did not significantly increase sociability (social interaction test) or induce spatial anxiety (elevated plus maze test). At a high dose (5 mg·kg À1 ), MXE induced transient analgesia (tail-flick and hot-plate test), decreased social interaction time (social interaction test) and reduced immobility time while increasing swimming activity (forced swim test), suggesting an antidepressant effect. Acute MXE administration did not affect self-grooming behaviour at any dose tested. Immunohistochemical analysis showed that behaviourally active doses of MXE (1 and 5 mg·kg À1 ) increased phosphorylation of ribosomal protein S6 in the medial prefrontal cortex and hippocampus. CONCLUSIONS AND IMPLICATIONSMXE differentially affected motor activity, behaviour and emotional states in rats, depending on the dose tested. As reported for ketamine, phosphorylation of the ribosomal protein S6 was increased in MXE-treated animals, thus providing a 'molecular snapshot' of rapid neuroadaptive molecular changes induced by behaviourally active doses of MXE. Abbreviations

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“…Valcyte − CIE female rats with intact NPCs showed enhanced freezing responses compared to CIE naïve rats and Valcyte + CIE rats during the baseline session that occurred at 72 hours of abstinence. Enhanced freezing during the baseline session is suggested to indicate anxiety-like behavior (Brandao et al , 2008; Pettersson et al , 2015), a phenotype that is demonstrated in female rats after chronic ethanol experience (Getachew et al , 2008). Valcyte prevented the rebound burst in NPCs in CIE female rats and reduced freezing responses during baseline session, demonstrating a role for NPCs generated during early abstinence in anxiety-like behavior.…”

Section: Discussionmentioning

confidence: 99%

Hippocampal neural progenitor cells play a distinct role in fear memory retrieval in male and female CIE rats

et al. 2018

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Adult male and female GFAP-TK transgenic rats experienced six weeks of chronic intermittent ethanol vapor inhalation (CIE). During the last week of CIE, a subset of male and female TK rats were fed with Valcyte to ablate neural progenitor cells (NPCs). Seventy-two hours after CIE cessation, all CIE and age matched ethanol naïve controls experienced auditory trace fear conditioning (TFC). Twenty-four hours later all animals were tested for cue-mediated retrieval in the fear context. Adult male CIE rats showed a significant burst in NPCs paralleled by reduction in fear retrieval compared to naïve controls and Valcyte treated CIE rats. Adult female CIE rats did not show a burst in NPCs and showed similar fear retrieval compared to naïve controls and Valcyte treated CIE rats, indicating that CIE-mediated impairment in fear memory and its regulation by NPCs was sex dependent. Valcyte significantly reduced Ki-67 and NeuroD labeled cells in the dentate gyrus (DG) in both sexes, demonstrating a role for NPCs in reduced fear retrieval in males. Valcyte prevented adaptations in GluN2A receptor expression and synaptoporin density in the DG in males, indicating that NPCs contributed to alterations in plasticity-related proteins and mossy fiber projections that were associated with reduced fear retrieval. These data suggest that DG NPCs born during withdrawal and early abstinence from CIE are aberrant, and could play a role in weakening long-term memory consolidation dependent on the hippocampus.

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Acute escitalopram but not contextual conditioning exerts a stronger “anxiogenic” effect in rats with high baseline “anxiety” in the acoustic startle paradigm

Cited by 9 publications

References 42 publications

Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing

Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing

Methoxetamine affects brain processing involved in emotional response in rats

Hippocampal neural progenitor cells play a distinct role in fear memory retrieval in male and female CIE rats

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