Grafelman Elaine M, Côté Bridgitte E, Vlach Lisa, Geise Ella, Padula G Nino, Wheeler Daniel S, Hearing Matthew, Mantsch John, Wheeler Robert A
Department of Biomedical Sciences, Marquette University, Milwaukee, WI 53233, USA.
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI, 53226.
bioRxiv. 2024 Aug 5:2024.08.05.606651. doi: 10.1101/2024.08.05.606651.
Dopamine release in the nucleus accumbens core (NAcC) has long been associated with the promotion of motivated behavior. However, inhibited dopamine signaling can increase behavior in certain settings, such as during drug self-administration. While aversive environmental stimuli can reduce dopamine, it is unclear whether such stimuli reliably engage this mechanism in different contexts. Here we compared the physiological and behavioral responses to the same aversive stimulus in different designs to determine if there is uniformity in the manner that aversive stimuli are encoded and promote behavior. NAcC dopamine was measured using fiber photometry in male and female rats during cocaine self-administration sessions in which an acutely aversive 90 dB white noise was intermittently presented. In a separate group of rats, aversion-induced changes in dopamine were measured in an escape design in which operant responses terminated aversive white noise. Aversive white noise significantly reduced NAcC dopamine and increased cocaine self-administration in both male and female rats. The same relationship was observed in the escape design, in which white noise reduced dopamine and promoted escape attempts. In both designs, the magnitude of the dopamine reduction predicted behavioral performance. While prior research demonstrated that pharmacologically reduced dopamine signaling can promote intake, this report demonstrates that this physiological mechanism is naturally engaged by aversive environmental stimuli and generalizable to non-drug contexts. These findings illustrate a common physiological signature in response to aversion that may promote both adaptive and maladaptive behavior.
伏隔核核心区（NAcC）的多巴胺释放长期以来一直与促进动机行为相关。然而，在某些情况下，如药物自我给药期间，多巴胺信号的抑制会增加行为。虽然厌恶的环境刺激会减少多巴胺，但尚不清楚这种刺激在不同情境下是否能可靠地激活这一机制。在此，我们在不同设计中比较了对相同厌恶刺激的生理和行为反应，以确定厌恶刺激编码和促进行为的方式是否具有一致性。在雄性和雌性大鼠进行可卡因自我给药期间，使用光纤光度法测量NAcC多巴胺，期间间歇性呈现90分贝的急性厌恶白噪声。在另一组大鼠中，在一种逃避设计中测量厌恶诱导的多巴胺变化，在该设计中，操作性反应可终止厌恶白噪声。厌恶白噪声显著降低了雄性和雌性大鼠的NAcC多巴胺水平，并增加了可卡因自我给药量。在逃避设计中也观察到了相同的关系，即白噪声降低了多巴胺水平并促进了逃避尝试。在两种设计中，多巴胺降低的幅度都预测了行为表现。虽然先前的研究表明，药理学上降低多巴胺信号可以促进摄入量，但本报告表明，这种生理机制是由厌恶的环境刺激自然激活的，并且可推广到非药物情境。这些发现说明了对厌恶反应的一种常见生理特征，这可能促进适应性和适应不良行为。
