Reciprocal interactions between MK-801, sleep deprivation and recovery in modulating rat behaviour
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Published on: October 11, 2018
Francisco Paulino Dubiela1, Melissa Fudoli Messias, Karin Di Monteiro Moreira
1Psychobiology Department, Universidade Federal de São Paulo, São Paulo, Brazil.
Abstract:
Increasing evidence indicates that sleep deprivation alters behavioural responses to various pharmacological agents which might be associated to changes in receptor systems. The present work addressed the effects of sleep deprivation and recovery on behavioural changes induced by MK-801, and investigated whether such effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an open field arena and elevated plus maze. A separate set of animals was sacrificed for [³H]MK-801 binding analysis in 40 brain regions. MK-801-induced hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD-induced increase in grooming was antagonized by the drug. Anxiolytic effects of 0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant differences among groups were found in NMDAR binding. These findings indicate that the combined effects of MK-801 and sleep deprivation and recovery interact in a complex fashion to affect rat behaviour. They further suggest that such effects cannot be attributed to altered NMDAR binding in brain.
Insights
Sleep deprivation alters behavioral responses to MK-801 in rats, with recovery sleep enhancing some effects. These behavioral changes are not linked to alterations in N-methyl-D-aspartate receptor (NMDAR) binding.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Sleep Research
Background:
- Sleep deprivation is known to affect behavioral responses to drugs.
- The N-methyl-D-aspartate receptor (NMDAR) system is implicated in mediating behavioral effects of various substances.
- The impact of sleep deprivation and subsequent recovery on MK-801-induced behaviors and NMDAR binding remains unclear.
Purpose of the Study:
- To investigate the effects of sleep deprivation (SD) and sleep recovery (SR) on behavioral changes induced by MK-801 in rats.
- To determine if these behavioral alterations are associated with changes in NMDAR binding.
Main Methods:
- Male Wistar rats underwent 96 hours of sleep deprivation (SD) or sleep deprivation followed by 24 hours of recovery (SR).
- Animals were administered MK-801 (0.05, 0.10, or 0.20 mg/kg) or saline and tested in open field and elevated plus maze paradigms.
- NMDAR binding was assessed using [³H]MK-801 autoradiography in 40 brain regions.
Main Results:
- Sleep recovery (SR) facilitated MK-801-induced hyperlocomotion in a dose-dependent manner.
- Sleep deprivation (SD) antagonized the increase in grooming behavior induced by MK-801.
- The anxiolytic effects of MK-801 were not significantly altered by sleep deprivation or recovery.
- No significant differences in NMDAR binding were observed across experimental groups.
Conclusions:
- Sleep deprivation and recovery interact complexly with MK-801 to modulate rat behavior.
- The observed behavioral effects of MK-801 under conditions of sleep manipulation are not attributable to changes in NMDAR binding.
