Continuous home cage monitoring of activity and sleep in mice during repeated paroxetine treatment and discontinuation.

Autor: Collins HM; University Department of Pharmacology, Oxford, UK.; University Department of Experimental Psychology, Oxford, UK., Pinacho R; University Department of Pharmacology, Oxford, UK.; University Department of Experimental Psychology, Oxford, UK., Tam SKE; Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford, OX1 3QU, UK., Sharp T; University Department of Pharmacology, Oxford, UK., Bannerman DM; University Department of Experimental Psychology, Oxford, UK., Peirson SN; Sleep and Circadian Neuroscience Institute (SCNi), Nuffield Department of Clinical Neurosciences, Kavli Institute for Nanoscience Discovery, Dorothy Crowfoot Hodgkin Building, South Parks Road, Oxford, OX1 3QU, UK. stuart.peirson@eye.ox.ac.uk.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2023 Nov; Vol. 240 (11), pp. 2403-2418. Date of Electronic Publication: 2023 Aug 16.
DOI: 10.1007/s00213-023-06442-3
Abstrakt: Rationale: Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation.
Objectives: We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice.
Methods: Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system.
Results: Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation.
Conclusions: This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms.
(© 2023. The Author(s).)
Databáze: MEDLINE
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