Carvalho, C.; Silva, F. E.; Carvalho, M.; Lima, J. E. C.; Chaves Filho, A. J.; Fries, G.; Sobreira-Neto, M.; Costa, D.; Fonteles, M.; Macedo, D. S.

Temperament may influence mood disorder risk under sleep disturbances. Using high- and low-exploratory rats as a temperament model, we examined the effects of paradoxical sleep deprivation (PSD) on mood behaviors, neuroinflammation, oxidative stress, clock genes, and dopamine receptor expression. Eighty male Wistar rats were screened for exploratory activity, while 20 were classified as high (HE) and 21 as low (LE) exploratory based on open-field performance. HE and LE rats were subjected to PSD or remained undisturbed (controls). Behavioral assessments included impulsivity, risk-taking, anhedonia, and forced swim test (FST) performance. Neurobiological analyses measured hippocampal lipid peroxidation, pro-inflammatory markers (IL-6, TLR4), gene expression of Clock, Tph2, Tdo2, and protein expression of D1, and D2, which regulate, respectively, circadian rhythms, serotonin synthesis, tryptophan metabolism, and dopaminergic signaling, key pathways implicated in mood disorders. HE rats showed increased impulsivity, risk-taking, and exploratory behaviors, resembling mania, while LE rats exhibited avoidance. PSD intensified these traits, heightening risk-taking in HE rats and inducing depressive-like behaviors in LE rats, including anhedonia and FST immobility linked to reduced Tph2 expression. Both groups had post-PSD working memory deficits. Neurobiologically, HE+PSD rats showed increased lipid peroxidation, neuroinflammation (IL-6, TLR4), and upregulation of Clock and DRD1 genes, while LE+PSD rats had elevated hippocampal Tdo2 expression. Temperament shapes PSD-induced behavioral and neurobiological effects. HE rats showed mania-like traits, while LE rats exhibited depressive behaviors. PSD impaired working memory in both. Oxidative stress, inflammation, and gene expression changes highlight distinct vulnerabilities and potential therapeutic targets for mood disorders.