AT1 Receptors Mediate the Effects of Cold Stress and Amphetamine on Neurocognitive Performance

Objectives In this work, we aimed to evaluate whether Amph exposure modifies the future neurocognitive response to cold stress, an environmental cue, and the possible role of the AT1-R. Methods Male Wistar rats received AT1-R blocker (Candesartan)/Vehicle from day 0 to 5, and Amph/Saline from day 6 to 10. After seven days of withdrawal, the animals were exposed to a cold challenge (4°C for 4 h) and tested for working and long-term memory. Results Cold challenge reversed the Amph-induced working memory deficit. Previous Amph exposure blunted the interference of cold stress on long-term memory consolidation. Blood adrenaline and glucose levels were increased in the Amph-treated animals after cold stress and/or test exposure. Remarkably, the AT1-R blockade prevented all these alterations induced by Amph exposure and elicited by cold-challenge. Conclusions Our results indicate that Amph-induced neuroadaptations exhibit a wide range of responses to catecholamine-releasing stimuli, including pharmacological and non-pharmacological challenges and environmental conditions involving the AT1-R.