Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats.

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY International Journal of Neuropsychopharmacology Pub Date : 2024-10-01 DOI:10.1093/ijnp/pyae048

Sierra J Stringfield, Erin K Kirschmann, Mary M Torregrossa

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Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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成年雄性大鼠的工作记忆能力可预测可卡因和大麻素的觅药行为，但不会减少这种行为。

背景：认知缺陷反映出执行功能受损，通常与精神疾病（包括药物使用）有关。认知训练可促进前额叶皮层的神经可塑性，增强执行控制能力，缓解吸毒导致的认知能力下降，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，减少寻求毒品的行为。我们研究了工作记忆训练是否能提高前额叶皮层的BDNF水平，以及这种训练是否能预测或防止可卡因或大麻素寻求行为：方法：训练成年雄性大鼠完成 "简单 "或 "复杂 "版本的延迟匹配到样本工作记忆任务。然后，大鼠自行服用可卡因或合成大麻素 WIN55,212-2，并在戒断期间接受诱导药物寻求测试。对前额叶皮层和海马背侧的组织进行了 BDNF 蛋白表达分析：结果：工作记忆任务训练提高了边缘前额叶皮层的内源性 BDNF 蛋白水平，但没有提高海马背侧的内源性 BDNF 蛋白水平。工作记忆训练对两种药物的自我给药均无影响，但可预测戒断期间WIN自我给药和可卡因寻求的程度：这些结果表明，工作记忆训练能促进内源性BDNF，但不会改变寻求毒品或服用毒品的行为。然而，药物暴露前认知表现的个体差异可能预示着未来药物使用的脆弱性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Neuropsychopharmacology 医学-精神病学

CiteScore

8.40

自引率

2.10%

发文量

230

审稿时长

4-8 weeks

期刊介绍： The central focus of the journal is on research that advances understanding of existing and new neuropsychopharmacological agents including their mode of action and clinical application or provides insights into the biological basis of psychiatric disorders and thereby advances their pharmacological treatment. Such research may derive from the full spectrum of biological and psychological fields of inquiry encompassing classical and novel techniques in neuropsychopharmacology as well as strategies such as neuroimaging, genetics, psychoneuroendocrinology and neuropsychology.