Department of Neuroscience, University of Minnesota, Twin Cities, Minneapolis, MN, 55455, USA.
Medical Discovery Team On Addiction, University of Minnesota, Twin Cities, Minneapolis, MN, 55455, USA.
Psychopharmacology (Berl). 2022 Sep;239(9):2885-2901. doi: 10.1007/s00213-022-06174-w. Epub 2022 Jun 16.
The anatomical, structural, and functional adaptations that occur in the brain during adolescence are thought to facilitate improvements in decision-making functions that are known to occur during this stage of development. The mechanisms that underlie these neural adaptations are not known, but deviations in developmental trajectories have been proposed to contribute to the emergence of mental illness, including addiction. Direct evidence supporting this hypothesis, however, has been limited. Here, we used a recently developed reversal-learning protocol to investigate the predictive relationship between adolescent decision-making trajectories and cocaine-taking behaviors in adulthood. Decision-making functions in the reversal-learning task were assessed throughout adolescence and into adulthood in male and female Long-Evans rats. Trial-by-trial choice data was fitted with a reinforcement-learning model to quantify the degree to which choice behavior of individual rats was influenced by rewarded (e.g., ∆ parameter) and unrewarded (e.g., ∆ parameter) outcomes. We report that reversal-learning performance improved during adolescence and that this was due to an increase in value updating for rewarded outcomes (e.g., ∆ parameter). Furthermore, the rate of change in the ∆ parameter predicted individual differences in the ∆ parameter and, notably, cocaine-taking behaviors in adulthood: Rats that had a shallower adolescent trajectory were found to have a lower ∆ parameter and greater cocaine self-administration in adulthood. These data indicate that adolescent development plays a critical role in drug use susceptibility. Future studies aimed at understanding the neurobiological mechanisms that underlie these age-related changes in decision-making could provide new insights into the biobehavioral mechanisms mediating addiction susceptibility.
青春期大脑中发生的解剖、结构和功能适应被认为促进了决策功能的改善，而这些决策功能在发育的这个阶段是已知会发生的。这些神经适应的机制尚不清楚，但发育轨迹的偏差被认为导致了精神疾病的出现，包括成瘾。然而，支持这一假设的直接证据是有限的。在这里，我们使用了一种新开发的反转学习协议来研究青春期决策轨迹与成年后可卡因使用行为之间的预测关系。在雄性和雌性长耳大仓鼠的整个青春期和成年期，我们在反转学习任务中评估了决策功能。通过强化学习模型拟合逐次选择数据，以量化个体大鼠的选择行为受奖励（例如，∆参数）和非奖励（例如，∆参数）结果影响的程度。我们报告说，反转学习表现随着青春期的发展而提高，这是由于奖励结果的价值更新（例如，∆参数）增加所致。此外，∆参数的变化率预测了个体在成年期的∆参数差异，特别是可卡因使用行为：具有较浅的青春期轨迹的大鼠被发现具有较低的∆参数和更大的可卡因自我给药。这些数据表明，青春期发育在药物使用易感性中起着关键作用。未来旨在理解决策中这些与年龄相关的变化背后的神经生物学机制的研究，可能会为成瘾易感性的生物行为机制提供新的见解。
