Hippocampal-hypothalamic lipid homeostasis and glial modulation by tramadol during sleep deprivation in periadolescent rats

Non-medical tramadol use may occur among individuals who restrict sleep to sustain alertness, physical activity, or occupational performance. However, the effects of tramadol exposure during repeated sleep deprivation remain poorly understood. This study investigated whether sleep deprivation modifies tramadol-associated behavioural and neurobiological alterations in female periadolescent rats. Sixty female periadolescent Wistar rats were assigned to control, sleep deprivation, long-term tramadol, short-term tramadol, sleep deprivation plus long-term tramadol, and sleep deprivation plus short-term tramadol with recovery groups. Animals were assessed for behavioural performance, hippocampal and hypothalamic lipid profile, malondialdehyde, NF κB p65, apolipoprotein E, GFAP, and IBA1 immunoreactivity. Sleep deprivation alone impaired working memory and social interaction, altered lipid metabolism, increased oxidative and inflammatory markers, reduced apolipoprotein E, and increased glial marker expression. Combined tramadol and sleep deprivation exposure did not produce an additive worsening pattern and was associated with partial attenuation of several sleep deprivation-related alterations. These findings indicate that sleep deprivation alters the neurobiological response observed following tramadol exposure. The results do not support tramadol use during sleep loss or indicate neuroprotective effects. Further studies using objective sleep monitoring and mechanistic approaches are required. Not applicable.