AT1 receptors mediate the effects of cold stress and amphetamine on neurocognitive performance.

Brain angiotensin II (Ang II) modulates catecholamine neurotransmission via its AT1 receptors (AT1-R) and plays a critical role in neurocognitive processes. We previously showed that amphetamine (Amph) exposure induced cognitive alterations, many times unmasked by further Amph or Ang II challenge administration. 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. Male Wistar rats received AT1-R blocker (Candesartan)/Vehicle from day 0 to 5, and Amph/Saline from day 6 to 10. After 7 days of withdrawal, the animals were exposed to a cold stress challenge (4 °C for 4 h) and tested for working and long-term memory. Cold stress reversed the Amph-induced working memory deficit, while 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 the alterations induced by Amph exposure and elicited by cold-challenge. Our results indicate that Amph-induced neuroadaptations exhibit a wide range of responses to a catecholamine-releasing stimuli, including pharmacological or non-pharmacological challenges, such as environmental conditions, involving the AT1-R.