Do greater levels of in-cage waking inactivity in laboratory mice reflect a spontaneous depression-like symptom? A pharmacological investigation

Fureix, Carole; Trevarthen, Anna; Finnegan, Emily M.; Bučková, Katarína; Paul, Elizabeth S.; Mendl, Michael

doi:10.1016/j.pbb.2021.173311

Cited by 14 publications

(18 citation statements)

References 58 publications

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“…We also observe strong relationships between measures of locomotion or inactivity and depressive‐like behaviour, supporting the importance of locomotor function in depressive outcomes (and its utility as a behavioural measure). Inactivity has been linked to depression‐like states in mice (Fureix et al, 2016, 2022), and increased activity is known to improve stress resilience (Arida & Teixeira‐Machado, 2021; Mul et al, 2018) and is anti‐depressive in MDD (Brüchle et al, 2021; Schuch et al, 2016). In contrast, no significant change in thigmotaxis (peripheral: centre square entries) was detected in models studied here, nor any relationships between this measure and other behaviours or CNS genes.…”

Section: Discussionmentioning

confidence: 99%

Central and cardiac stress resilience consistently linked to integrated immuno‐neuroendocrine responses across stress models in male mice

Helman

Headrick

Peart

et al. 2022

Eur J of Neuroscience

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Stress resilience, and behavioural and cardiovascular impacts of chronic stress, are theorised to involve integrated neuro‐endocrine/inflammatory/transmitter/trophin signalling. We tested for this integration, and whether behaviour/emotionality, together with myocardial ischaemic tolerance, are consistently linked to these pathways across diverse conditions in male C57Bl/6 mice. This included Restraint Stress (RS), 1 h restraint/day for 14 days; Chronic Unpredictable Mild Stress (CUMS), seven stressors randomised over 21 days; Social Stress (SS), 35 days social isolation with brief social encounters in final 13 days; and Control conditions (CTRL; un‐stressed mice). Behaviour was assessed via open field (OFT) and sucrose preference (SPT) tests, and neurobiology from frontal cortex (FC) and hippocampal transcripts. Endocrine factors, and function and ischaemic tolerance in isolated hearts, were also measured. Model characteristics ranged from no behavioural or myocardial changes with homotypic RS, to increased emotionality and cardiac ischaemic injury (with apparently distinct endocrine/neurobiological profiles) in CUMS and SS models. Highly integrated expression of HPA axis, neuro‐inflammatory, BDNF, monoamine, GABA, cannabinoid and opioid signalling genes was confirmed across conditions, and consistent/potentially causal correlations identified for (i) locomotor activity (noradrenaline, ghrelin; FC Crhr1, Tnfrsf1b, Il33, Nfkb1, Maoa, Gabra1; hippocampal Il33); (ii) thigmotaxis (adrenaline, leptin); (iii) anxiety‐like behaviour (adrenaline, leptin; FC Tnfrsf1a; hippocampal Il33); (iv) depressive‐like behaviour (ghrelin; FC/hippocampal s100a8); and (v) cardiac stress‐resistance (noradrenaline, leptin; FC Il33, Tnfrsf1b, Htr1a, Gabra1, Gabrg2; hippocampal Il33, Tnfrsf1a, Maoa, Drd2). Data support highly integrated pathway responses to stress, and consistent adipokine, sympatho‐adrenergic, inflammatory and monoamine involvement in mood and myocardial disturbances across diverse conditions.

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Section: Discussionmentioning

confidence: 99%

Central and cardiac stress resilience consistently linked to integrated immuno‐neuroendocrine responses across stress models in male mice

Helman

Headrick

Peart

et al. 2022

Eur J of Neuroscience

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“…Experiment 2 had a complementary aim: to improve the accuracy of IBA as an indicator of poor welfare. Current ethogram descriptions of IBA only require that a mouse remains motionless with eyes open for 3 seconds or more [14,15,17]. Despite being simple and objective, this broad description probably leads to the classification of diverse forms of inactivity as IBA, including normal resting behaviour.…”

Section: Introductionmentioning

confidence: 99%

“…These tests aim to approximate the ways that clinically depressed humans can have passive responses to adversity (due to beliefs that desired outcomes are unlikely, aversive outcomes are likely, and one's actions have no impact on such consequences [35,36]). Finally, recent research has also shown that IBA is reduced by an antidepressant (venlafaxine [17]).…”

Section: Introductionmentioning

confidence: 99%

“…Here, some individuals spend excessive time simply lying motionless, but with their eyes are open (indicating that they are awake) during the dark, active phase of their circadian rhythm. This ‘inactive-but-awake’ (IBA) behaviour reliably occurs at higher levels in conventional ‘shoebox’ cages than in well-resourced, environmentally enriched housing [14–17] (the label ‘well-resourced’ being applied hereafter to describe complex environments, since the more common term ‘enriched’ implies conditions do more than meet basic needs; see [18,19,20] for further discussion). Such housing effects provide construct validity for the use of IBA as an indicator of negative affect, since it is well established that these barren conditions (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Waking inactivity as a welfare indicator in laboratory mice: investigating postures, facial expressions and depression-like states

et al. 2022

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Animal welfare assessment relies on valid and practical indicators of affect. In mice, the most widely used research vertebrates, lying still with eyes open, inactive-but-awake (IBA) in the home cage, has potential to be one such indicator. IBA is elevated in barren, conventional housing compared with well-resourced, enriched housing, and predicts immobility in Forced Swim Tests, a common measure of ‘helplessness’ in depression research. In Experiment 1, using females from three strains (C57BL/6, Balb/c and DBA/2), we first replicated past findings, confirming higher levels of IBA in conventional cages and a positive relationship between IBA and helplessness. We then extended this research to three other signs of depression: changes in weight and sleep, and reduced hippocampal volume. Here, IBA positively covaried with body mass index, with sleep in DBA/2s and conventionally housed BALB/cs, and negatively covaried with hippocampal volume in conventionally housed C57BL/6s. In Experiment 2, we sought to refine the phenotype of IBA to improve its accuracy as a welfare indicator. Here, scoring IBA performed in hunched postures appeared to improve its accuracy as an indicator in Balb/c mice. Additional research is now needed to further refine the phenotype of IBA and to confirm whether it reflects states consistent with depression, or instead other underlying poor welfare conditions.

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“…Studies across species show that housing animals in environment with insufficient enrichment, i.e., with limited opportunities to fulfil natural behaviours, impairs their welfare ( Vitalo et al, 2012 , Zhang et al, 2021 , Fureix et al, 2022 ). In pigs, barren housing has been found to cause negative affective states, increase occurrence of undesirable behaviours (e.g., tail biting), decrease inactivity, and impair immunity ( Bolhuis et al, 2005 , Douglas et al, 2012 , Telkänranta et al, 2014 , van Dixhoorn et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Consequences of timing of organic enrichment provision on pig performance, health and stress resilience after weaning and regrouping

Bučková¹,

Muns²,

Cerón³

et al. 2022

animal

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Do greater levels of in-cage waking inactivity in laboratory mice reflect a spontaneous depression-like symptom? A pharmacological investigation

Cited by 14 publications

References 58 publications

Central and cardiac stress resilience consistently linked to integrated immuno‐neuroendocrine responses across stress models in male mice

Central and cardiac stress resilience consistently linked to integrated immuno‐neuroendocrine responses across stress models in male mice

Waking inactivity as a welfare indicator in laboratory mice: investigating postures, facial expressions and depression-like states

Consequences of timing of organic enrichment provision on pig performance, health and stress resilience after weaning and regrouping

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