Constitutive depletion of brain serotonin differentially affects rats’ social and cognitive abilities

Alonso, Lucille; Peeva, Polina; Stasko, Sabrina; Bäder, Michael; Alenina, Natalia; Winter, York; Rivalan, Marion

doi:10.1016/j.isci.2023.105998

Cited by 8 publications

(19 citation statements)

References 141 publications

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“…For the RGT, operant cages were equipped with four nose-poke holes arranged in two pairs (5 cm between holes) on each sides of the curved wall (12.5 cm between pairs). The training and testing procedures (Alonso et al, 2023, 2019; Rivalan et al, 2013, 2009) were adapted to the treatment period required by the tetO system. The training started at day 1 of the Dox treatment (Fig.1).…”

Section: Methodsmentioning

confidence: 99%

“…The animals were tested in the reversed-RGT 48 hours after the RGT. For this test the two disadvantageous options were spatially switched with the two advantageous options (Alonso et al, 2023(Alonso et al, , 2019Rivalan et al, 2013). A flexibility score was calculated as the preference during reversed-RGT for the location of the non-preferred option during the RGT.…”

Section: Reversed-rgtmentioning

confidence: 99%

“…For the PDT, operant cages were equipped with two nose-poke holes on each outer side of the curved wall (25 cm between holes). The protocol was adapted to reduce its overall duration (Alonso et al, 2023) due to the pharmacological treatment. One hole (NP1) was associated with a small and sure reward (1 pellet), the second one (NP5) was associated with a large and uncertain reward (5 pellets) (Koot et al, 2012).…”

Section: Probability Discounting Task (Pdt)mentioning

confidence: 99%

“…Healthy poor decision makers are consistently found, between labs (Daniel et al, 2017; Mu et al, 2015), across strains (WH and DA (Alonso et al, 2019), SD (this paper and (Daniel et al, 2017; Mu et al, 2015) and Long Evans –unpublished data–) and species (mouse (Pittaras et al, 2016), primate and monkey (Proctor et al, 2014)). Healthy rats’ poor decision makers present a unique combination of preserved and impaired neurological and behavioral characteristics (Alonso et al, 2023, 2019; Rivalan et al, 2013, 2011, 2009). They express high reward-seeking and risk-seeking behavior, inflexibility, and a tendency to dominant behavior together with normal control of cognitive impulsivity and economical risk taking and a normal social everyday life (Alonso et al, 2019; Rivalan et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Poor decision making and sociability impairment following central serotonin reduction in inducible TPH2-knockdown rats

Alonso,

Peeva,

Fernández del valle Alquicira

et al. 2024

Preprint

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Serotonin is an essential neuromodulator for mental health and animals' socio-cognitive abilities. However, we previously found that a constitutive depletion of central serotonin did not impair rat cognitive abilities in stand-alone tests. Here we investigated how a mild and acute decrease of brain serotonin would affect rats' cognitive abilities. Using a novel rat model of inducible serotonin depletion via the genetic knock-down of tryptophan hydroxylase 2 (TPH2), we achieved 20% decrease of serotonin levels in the hypothalamus after three weeks of non-invasive oral doxycycline administration. Decision making in the Rat Gambling Task and the Probability Discounting Task, cognitive flexibility and social recognition memory were tested in low-serotonin (Tph2-kd) and control rats. Our results showed that the Tph2-kd rats were more prone to choose disadvantageously on the long term (poor decision making) and that only the low-serotonin poor decision makers were more sensitive to probabilistic discounting and had poorer social recognition memory than other low-serotonin and control individuals. Flexibility was unaffected by the acute brain serotonin reduction. Poor social recognition memory was the most central characteristic of the behavioral network of low-serotonin poor decision makers, suggesting a key role of social recognition in expression of their profile. The acute decrease of brain serotonin appeared to specifically amplify cognitive impairments of the subgroup of individuals also identified as poor decision makers in the population. This study highlights the great opportunity Tph2-kd rat model offers to study inter-individual susceptibilities to develop cognitive impairment following mild variations of brain serotonin in otherwise healthy individuals. These transgenic and differential approaches together could be critical for the identification of translational markers and vulnerabilities in the development of mental disorders.

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Section: Methodsmentioning

confidence: 99%

Section: Reversed-rgtmentioning

confidence: 99%

Section: Probability Discounting Task (Pdt)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Poor decision making and sociability impairment following central serotonin reduction in inducible TPH2-knockdown rats

Alonso,

Peeva,

Fernández del valle Alquicira

et al. 2024

Preprint

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“…The Visible Burrow System (VBS) is a semi-natural habitat first developed in rats (Blanchard and Blanchard, 1989) and more recently in mice (Arakawa et al, 2007, Pobbe et al, 2012, Bove et al, 2018 where ethological aspects (e.g. day/night fluctuation of activity spatial distribution, place preference) and social and non-social behaviours of group-housed, freelymoving individuals can be continuously observed and quantified (Alonso et al, 2020(Alonso et al, , 2023.…”

Section: Introductionmentioning

confidence: 99%

Serotonin drives aggression and social behaviours of laboratory mice in a semi-natural environment

Rivalan,

Alonso,

Mosienko

et al. 2024

Preprint

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Aggression is an adaptive social behaviour crucial for the stability and prosperity of social groups. When uncontrolled, aggression leads to pathological violence that disrupts group structure and individual well-being. The comorbidity of uncontrolled aggression across different psychopathologies makes it a potential endophenotype of mental disorders with the same neurobiological substrates. Serotonin plays a critical role in the regulation of impulsive and aggressive behaviours, and mice lacking brain serotonin, due to the ablation of a rate-limiting enzyme of serotonin synthesis (Tryptophan hydroxylase 2, TPH2), are a potential model of pathological aggression. Home cage monitoring allows for the continuous observation and quantification of social and non-social behaviours in group-housed, freely-moving mice. Using an ethological approach, we investigated the impact of central serotonin ablation on everyday expression of social and non-social behaviours and their correlations in undisturbed, group-living Tph2-deficient and wildtype mice. By training a machine learning algorithm on behavioural time series, allogrooming, struggling at feeder and eating emerged as key behaviours dissociating one genotype from the other. Although Tph2-deficient mice showed characteristics of pathological aggression and decreased communication compared to wildtype animals, they still showed affiliative behaviours to normal levels. Altogether, such distinct and dynamic phenotype of Tph2-deficient mice influenced the group's structure and the dynamic of its hierarchical organization, which emerged later. These aspects were analysed using social network analysis and the Glicko rating methods. This study demonstrates the importance of the ethological approach for understanding the global impact of pathological aggression on different aspects of life, both at the individual and the group level. Home cage monitoring allows the observation of the natural behaviours of the mice in a semi-natural habitat and provides an accurate representation of real-world phenomena and pathological mechanisms. The results of this study provide insights into the neurobiological substrate of pathological aggression and their potential role in complex brain disorders.

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Early‐life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions

Mashahadi,

Saadati,

Ghaheri Fard

2024

Intl J of Devlp Neuroscience

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Serotonin is a monoamine neurotransmitter that plays a main role in regulating physiological and cognitive functions. Serotonergic system dysfunction is involved in the etiology of various psychiatric and neurological disorders. Therefore, the present study was designed to investigate the effects of early‐life serotonin depletion on cognitive disorders caused by sleep deprivation. Serotonin was depleted by para‐chlorophenylalanine (PCPA, 100 mg/kg, s.c.) at postnatal days 10–20, followed by sleep deprivation‐induced through the multiple platform apparatus for 24 h at PND 60. After the examination of the novel object recognition and passive avoidance memories, the hippocampi and prefrontal cortex were dissected to examine the brain‐derived neurotrophic factor (BDNF) mRNA expression by PCR. Our findings showed that postnatal serotonin depletion and sleep deprivation impaired the novel object recognition and passive avoidance memories and changed the BDNF levels. In the same way, the serotonin depletion in early life before sleep deprivation exacerbated the harmful effects of sleep deprivation on cognitive function and BDNF levels. It can be claimed that the serotonergic system plays a main role in the modulation of sleep and cognitive functions.

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Constitutive depletion of brain serotonin differentially affects rats’ social and cognitive abilities

Cited by 8 publications

References 141 publications

Poor decision making and sociability impairment following central serotonin reduction in inducible TPH2-knockdown rats

Poor decision making and sociability impairment following central serotonin reduction in inducible TPH2-knockdown rats

Serotonin drives aggression and social behaviours of laboratory mice in a semi-natural environment

Early‐life manipulation of the serotonergic system exacerbates the harmful effects of sleep deprivation on cognitive functions

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