Lämpötilaerojen merkitys: Farmakologisten hoitojen ja kroonisen stressin vaikutukset hiirten aivojen ja kehon lämpötilan dynamiikkaan

Major depressive disorder (MDD) remains a significant global health challenge, with a substantial percentage of patients failing to respond to conventional treatments. Emerging evidence links temperature dysregulation to depression and antidepressant response, suggesting that thermoregulatory processes may represent both a physiological biomarker and a potential therapeutic target. This thesis investigates the relationship between brain and core temperature dynamics, chronic stress, and antidepressant action through three distinct experiments using in vivo mouse models. Firstly, we screened the acute effects of various psychoactive compounds on both brain and core temperature. We found that several pharmacologically distinct agents induced strong and significant dose-dependent hypothermic effects, including conventional antidepressants (amitriptyline, fluoxetine), serotonergic psychedelics (dimethyltryptamine, psilocybin), 5-AMP and sedatives (dexmedetomidine, zolpidem). Conversely, atipamezole, D-amphetamine, escitalopram, ketamine, and lithium chloride did not significantly alter temperature. Secondly, we sought to assess the therapeutic efficacy of body-temperature-modulating interventions in chronic stress. To achieve this, we used the chronic unpredictable mild stress (CUMS) paradigm followed by a single session of dexmedetomidine-induced hypothermia and non-pharmacological whole-body hyperthermia (WBH). Subsequently, we conducted a comprehensive behavioural battery evaluating anxiety-like, social, and depression-like behaviour, and we found that our CUMS model was not effective in creating a robust behavioural phenotype, which limited the evaluation of the effects of temperature-modulating interventions. Finally, in the diurnal rhythm experiment we utilised continuous brain and core temperature recordings to investigate how chronic stress influences diurnal thermal rhythm during 1 week of baseline and 3 weeks of CUMS exposure. Our data revealed that CUMS exposure leads to a blunted diurnal temperature rhythm, particularly decreasing the difference between active and inactive temperatures, the biggest effect showing between weeks 2 and 3 of CUMS. In conclusion, these results demonstrate that hypothermic effects are common across mechanistically distinct psychoactive drugs, and that chronic stress alters diurnal temperature rhythmicity, most strikingly by blunting the dark-light brain temperature amplitude. Together, these findings underline the importance of measuring temperature as an experimental variable as well as underscore the need for refined preclinical models to further dissect the mechanisms underlying these temperature-related effects.