| 1. |
- Hagsäter, S Melker, et al.
(författare)
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A Complex Impact of Systemically Administered 5-HT2A Receptor Ligands on Conditioned Fear
- 2021
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press (OUP). - 1461-1457 .- 1469-5111. ; 24:9, s. 749-757
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Tidskriftsartikel (refereegranskat)abstract
- Background: Though drugs binding to serotonergic 5-HT2A receptors have long been claimed to influence human anxiety, it remains unclear if this receptor subtype is best described as anxiety promoting or anxiety dampening. Whereas conditioned fear expressed as freezing in rats is modified by application of 5-HT2A-acting drugs locally into different brain regions, reports on the effect of systemic administration of 5-HT2A receptor agonists and 5-HT2A antagonists or inverse agonists on this behavior remain sparse. Methods: We assessed the possible impact of systemic administration of 5-HT2A receptor agonists, 5-HT2A receptor inverse agonists, and a selective serotonin reuptake inhibitor (SSRI)-per se or in combination-on the freezing displayed by male rats when re-exposed to a conditioning chamber in which they received foot shocks 7 days earlier. Results: The 5-HT2A receptor agonists psilocybin and 25CN-NBOH induced a reduction in conditioned fear that was countered by pretreatment with 5-HT2A receptor inverse agonist MDL 100907. While both MDL 100907 and another 5-HT2A receptor inverse agonist, pimavanserin, failed to impact freezing per se, both compounds unmasked a robust fear-reducing effect of an SSRI, escitalopram, which by itself exerted no such effect. Conclusions: The results indicate that 5-HT2A receptor activation is not a prerequisite for normal conditioned freezing in rats but that this receptor subtype, when selectively over-activated prior to expression, exerts a marked fear-reducing influence. However, in the presence of an SSRI, the 5-HT2A receptor, on the contrary, appears to counter an anti-freezing effect of the enhanced extracellular serotonin levels following reuptake inhibition.
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| 2. |
- Bäckström, Daniel, 1985, et al.
(författare)
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Measurement of the size distribution, volume fraction and optical properties of soot in an 80 kW propane flame
- 2017
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Ingår i: Combustion and Flame. - : Elsevier BV. - 0010-2180 .- 1556-2921. ; 186, s. 325-334
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Tidskriftsartikel (refereegranskat)abstract
- This work presents measurements of the size distribution, volume fraction, absorption and scattering coefficients of soot in an 80 kW swirling propane-fired flame. Extractive measurements were performed in the flame using an oil-cooled particle extraction probe. The particle size distribution was measured with a Scanning Mobility Particle Sizer (SMPS) and the optical properties were measured using a Photo Acoustic Soot Spectrometer (PASS-3). A detailed radiation model was used to examine the influence of the soot volume fraction on the particle radiation intensity. The properties of the gas were calculated with a statistical narrow-band model and the particle properties were calculated using Rayleigh theory with four different complex indices of refraction for soot particles. The modelled radiation was compared with measured total radiative intensity, the latter which was measured with a narrow angle radiometer. The results show that the measured soot volume fraction yields particle radiation that corresponds well with the determined difference between gas and total radiation. This indicates that the presented methodology is capable of quantifying both the particle and gaseous radiation in a flame of technical size. (C) 2017 The Combustion Institute. Published by Elsevier Inc. All rights reserved.
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| 3. |
- Bäckström, Daniel, 1985, et al.
(författare)
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Particle composition and size distribution in coal flames - The influence on radiative heat transfer
- 2015
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Ingår i: Experimental Thermal and Fluid Science. - : Elsevier BV. - 0894-1777 .- 1879-2286. ; 64, s. 70-80
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Tidskriftsartikel (refereegranskat)abstract
- Radiative heat transfer in a 77 kWth swirling lignite flame has been studied. The aim is to characterize different particle types present in a coal flame and to determine their influence on the radiative heat transfer. The study combines extractive particle measurements, radiative intensity measurements and detailed radiation modelling. The size distribution of the extracted particles was measured with a low pressure impactor and some of the size fractions were analysed with SEM–EDX. The measured total radiative intensity is compared with the modelled intensity based on the particle measurements in the same cross-section of the flame. The particle properties were calculated with Mie theory and the gas properties with a statistical narrow-band model. The results show that the contribution of coal/char particles dominates the radiative heat transfer in the investigated cross-section of the flame. The methodology applied in this work shows promising results for characterization of particle radiation in flames of practical size.
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| 4. |
- Hagsäter, S Melker, et al.
(författare)
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Selective serotonin reuptake inhibition increases noise burst-induced unconditioned and context-conditioned freezing.
- 2019
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Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 31:1, s. 46-51
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Tidskriftsartikel (refereegranskat)abstract
- Whereas 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.Male 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.Noise 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.The 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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| 5. |
- Hagsäter, S Melker, et al.
(författare)
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Serotonin depletion reduces both acquisition and expression of context-conditioned fear.
- 2021
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Ingår i: Acta neuropsychiatrica. - : Cambridge University Press (CUP). - 1601-5215 .- 0924-2708. ; 33:3, s. 148-155
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Tidskriftsartikel (refereegranskat)abstract
- Whereas numerous experimental and clinical studies suggest a complex involvement of serotonin in the regulation of anxiety, it remains to be clarified if the dominating impact of this transmitter is best described as anxiety-reducing or anxiety-promoting. The aim of this study was to assess the impact of serotonin depletion on acquisition, consolidation, and expression of conditioned fear.Male Sprague-Dawley rats were exposed to foot shocks as unconditioned stimulus and assessed with respect to freezing behaviour when re-subjected to context. Serotonin depletion was achieved by administration of a serotonin synthesis inhibitor, para-chlorophenylalanine (PCPA) (300mg/kg daily×3), (i) throughout the period from (and including) acquisition to (and including) expression, (ii) during acquisition but not expression, (iii) after acquisition only, and (iv) during expression only.The time spent freezing was significantly reduced in animals that were serotonin-depleted during the entire period from (and including) acquisition to (and including) expression, as well as in those being serotonin-depleted during either acquisition only or expression only. In contrast, PCPA administrated immediately after acquisition, that is during memory consolidation, did not impact the expression of conditioned fear.Intact serotonergic neurotransmission is important for both acquisition and expression of context-conditioned fear.
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| 6. |
- Näslund, Jakob, et al.
(författare)
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Differences in anxiety-like behavior within a batch of wistar rats are associated with differences in serotonergic transmission, enhanced by acute sri administration, and abolished by serotonin depletion
- 2015
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Ingår i: International Journal of Neuropsychopharmacology. - : Oxford University Press (OUP). - 1461-1457 .- 1469-5111. ; 18:8, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: The anxiety-reducing effect of long-term administration of serotonin reuptake inhibitors is usually seen only in subjects with anxiety disorders, and such patients are also abnormally inclined to experience a paradoxical anxietyenhancing effect of acute serotonin reuptake inhibition. These unique responses to serotonin reuptake inhibitors in anxietyprone subjects suggest, as do genetic association studies, that inter-individual differences in anxiety may be associated with differences in serotonergic transmission. Methods: The one-third of the animals within a batch of Wistar rats most inclined to spend time on open arms in the elevated plus maze were compared with the one-third most inclined to avoid them with respect to indices of brain serotonergic transmission and how their behavior was influenced by serotonin-modulating drugs. Results: "Anxious" rats displayed higher expression of the tryptophan hydroxylase-2 gene and higher levels of the tryptophan hydroxylase-2 protein in raphe and also higher levels of serotonin in amygdala. Supporting these differences to be important for the behavioral differences, serotonin depletion obtained by the tryptophan hydroxylase-2 inhibitor p-chlorophenylalanine eliminated them by reducing anxiety in "anxious" but not "non-anxious" rats. Acute administration of a serotonin reuptake inhibitor, paroxetine, exerted an anxiety-enhancing effect in "anxious" but not "non-anxious" rats, which was eliminated by long-term pretreatment with another serotonin reuptake inhibitor, escitalopram. Conclusions: Differences in an anxiogenic impact of serotonin, which is enhanced by acute serotonin reuptake inhibitor administration, may contribute to differences in anxiety-like behavior amongst Wistar rats..
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| 7. |
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| 8. |
- Pettersson, Robert, 1985
(författare)
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Influence of serotonin on anxiety-like behavior in rat
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- It is well-established that serotonin is involved in the regulation of mood and behaviour, partly implied by the therapeutic effect of prolonged treatment with selective serotonin reuptake inhibitors (SSRI) on mood and anxiety disorders. However, the mechanisms behind the paradoxical exacerbation of anxiety described during initial treatment, as well as behind the therapeutic effects of prolonged treatment with SSRIs, remain poorly understood. In the research described in this thesis, the effects of different manipulations of the serotonin system on anxiety-related behaviour was studied in rat models of contextual conditioned fear. In Paper I, we investigated whether rats could be classified as more or less ‘anxious’ based on two behaviours, namely startle and freezing, and to what extent this baseline ‘anxiousness’ predicted subsequent startle and freezing behaviour in the response to acute administration of an SSRI, escitalopram, with or without further aggravation of fear by so-called contextual conditioned fear conditioning. Startle and freezing correlated and showed good inter-test stability before contextual conditioning and were both enhanced by escitalopram, where the enhancement of startle was more pronounced in animals with high startle and freezing before contextual conditioning. This resembles the clinical picture, in the sense that anxiety-prone patients can experience worsening of their anxiety symptoms during early medication with SSRIs. The work of Paper II evaluated whether startle and freezing in the model of Paper I were dependent on serotonin and whether sex was an important factor. Startle and freezing responses were assessed in male and female rats after treatment with a serotonin-depleting agent, para-chlorophenylalanine (PCPA), with or without prior contextual conditioning. The main finding, i.e. that PCPA reduced contextual conditioned freezing solely in male rats, thereby abolishing a sex difference in this parameter, indicates that both sex and serotonin can influence anxiety-like behaviour. In Paper III, the possible involvement of specific serotonin receptor subtypes for the effect of acute SSRI administration on contextual conditioned freezing was examined. Without exerting any effect on their own, the combination of a 5-HT2A receptor antagonist and escitalopram resulted in a pronounced reduction in freezing behaviour. A remarkable freezing reduction was also observed after administration of any of two agents normally causing a more robust increase in extracellular serotonin than do the SSRIs, i.e. 5-hydroxytryotophan (5-HTP) (a serotonin precursor) or fenfluramine (a serotonin releaser). It is suggested that the effect of 5-HT2A antagonism may be mediated by inhibition of negative feedback leading to higher extracellular serotonin, but it is also possible that it unmasks an anti-freezing effect of escitalopram by blocking freezing-promoting postsynaptic receptors normally activated by the SSRI. The possibility that the anti-freezing effect of escitalopram plus the 5-HT2A antagonist is mediated by postsynaptic 5-HT1A receptors was explored; however, this appeared not to be the case. The experiments described by Paper IV showed that long-term treatment with escitalopram reduced contextual freezing whereas acute escitalopram administered at a dose causing similar serum levels of the compound did not influence the behaviour. These results mirror the clinical situations and suggest this model as useful for studying mechanisms underlying the effect of short- versus long-term SSRI treatment. It remains unsolved whether the reduction in freezing by long-term SSRI treatment is caused by a negative or positive influence on extracellular serotonin level; since a powerful reduction of freezing may be obtained both by serotonin-reducing and serotonin-enhancing agents, neither of these options can be ruled out. The finding that the freezing-reduction caused by long-term SSRI could not be reversed by serotonin-enhancing treatment however favours the latter possibility. In conclusion, the experiments indicate (1) that there are notable similarities between the studied behaviours and human anxiety (2) that intact serotonergic transmission seems important for freezing behaviour and (3) that the 5-HT2A receptor seems to play an important role in the underlying mechanisms.
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| 9. |
- Pettersson, Robert, 1985, et al.
(författare)
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Serotonin depletion eliminates sex differences with respect to context-conditioned immobility in rat
- 2016
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Ingår i: Psychopharmacology. - : Springer Science and Business Media LLC. - 0033-3158 .- 1432-2072. ; 233:8, s. 1513-1521
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have shown that male rats display more anxiety-like behavior than females as assessed using the elevated plus maze and that serotonin depletion abolishes this difference by exerting an anxiolytic-like effect in males only. To compare male and female rats with respect to immobility and startle responses to sudden noise bursts after contextual fear conditioning and to explore to what extent any possible sex difference in this regard is influenced by serotonin depletion during testing (but not acquisition). In line with previous studies, males displayed more immobility following contextual conditioning induced by previous exposure to foot shocks than females. In males but not females, the immobility response was reduced by administration of the serotonin synthesis inhibitor para-chlorophenylalanine (PCPA) between shock exposure and testing, the consequence being that males and females no longer differed in this regard. Untreated males but not females displayed a negative correlation between fear-conditioned startle and immobility, suggesting that the latter behavior, when excessive, interferes with the former. In line with this assumption, the reduction in immobility following administration of PCPA in males coincided with an increase in startle that was not observed in females, hence revealing a sex difference in startle not seen in untreated controls. The greater display of context-conditioned immobility in males compared with females appears to be serotonin-dependent.
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| 10. |
- Suchankova, Petra, 1979, et al.
(författare)
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Personality traits and the R668Q polymorphism located in the MMP-9 gene.
- 2012
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Ingår i: Behavioural brain research. - : Elsevier BV. - 1872-7549 .- 0166-4328. ; 228:1, s. 232-5
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Tidskriftsartikel (refereegranskat)abstract
- Matrix metalloproteinases (MMPs) are enzymes involved in degradation of proteins in the extracellular matrix and have been shown to contribute to neuroinflammation by several mechanisms such as blood-brain barrier breakdown. Among the MMPs, MMP-9 (gelatinase B) has been suggested to be of relevance also for synaptic and behavioural plasticity. In order to explore the role of MMP-9 for mental functions a polymorphism in MMP-9 was analysed with respect to personality traits. The two studied populations consisted of women and men, respectively, both recruited from the population registry and assessed by means of the Karolinska Scales of Personality. The non-synonymous single nucleotide polymorphism (R668Q, rs17577) studied is located in the coding region of MMP-9 and is believed to affect the activity of the enzyme. The present study found that an amino acid change from arginine (R) to glutamine (Q) was associated with higher scores of the personality trait inhibition of aggression in the female population whilst this substitution was associated with higher scores of verbal aggression and irritability in men. These findings give support for an influence of MMP-9 on mental functions.
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