Department of Psychiatry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Department of Psychology and Counseling, Immaculata University, Immaculata, Pennsylvania, USA.
Int J Neuropsychopharmacol. 2024 Oct 1;27(10). doi: 10.1093/ijnp/pyae048.
Cognitive deficits reflecting impaired executive function are commonly associated with psychiatric disorders, including substance use. Cognitive training is proposed to improve treatment outcomes for these disorders by promoting neuroplasticity within the prefrontal cortex, enhancing executive control, and mitigating cognitive decline due to drug use. Additionally, brain derived neurotrophic factor (BDNF) can facilitate plasticity in the prefrontal cortex and reduce drug-seeking behaviors. We investigated whether working memory training could elevate BDNF levels in the prefrontal cortex and if this training would predict or protect against cocaine or cannabinoid seeking.
Adult male rats were trained to perform a "simple" or "complex" version of a delayed-match-to-sample working memory task. Rats then self-administered cocaine or the synthetic cannabinoid WIN55,212-2 and were tested for cued drug seeking during abstinence. Tissue from the prefrontal cortex and dorsal hippocampus was analyzed for BDNF protein expression.
Training on the working memory task enhanced endogenous BDNF protein levels in the prelimbic prefrontal cortex but not the dorsal hippocampus. Working memory training did not impact self-administration of either drug but predicted the extent of WIN self-administration and cocaine seeking during abstinence.
These results suggest that working memory training promotes endogenous BDNF but does not alter drug-seeking or drug-taking behavior. However, individual differences in cognitive performance before drug exposure may predict vulnerability to future drug use.
反映执行功能受损的认知缺陷通常与精神疾病有关，包括物质使用障碍。认知训练被认为可以通过促进前额叶皮层的神经可塑性、增强执行控制以及减轻因药物使用导致的认知衰退，从而改善这些疾病的治疗效果。此外，脑源性神经营养因子（BDNF）可以促进前额叶皮层的可塑性并减少药物寻求行为。我们研究了工作记忆训练是否可以提高前额叶皮层中的 BDNF 水平，以及这种训练是否可以预测或预防可卡因或大麻素的寻求。
成年雄性大鼠接受训练以执行延迟匹配样本工作记忆任务的“简单”或“复杂”版本。然后，大鼠自行给予可卡因或合成大麻素 WIN55,212-2，并在戒断期间测试线索诱导的药物寻求。从前额叶皮层和背侧海马体中分析 BDNF 蛋白表达。
工作记忆任务的训练增强了前额叶皮层的内源性 BDNF 蛋白水平，但不影响背侧海马体。工作记忆训练不会影响两种药物的自我给药，但预测了 WIN 自我给药和可卡因戒断期间寻求的程度。
这些结果表明，工作记忆训练促进内源性 BDNF，但不会改变药物寻求或药物摄取行为。然而，暴露于药物之前的认知表现的个体差异可能预测未来药物使用的易感性。
