Centro de Investigación Biomédica y Aplicada (CIBAP), Escuela de Medicina, Facultad de Ciencias Médicas, Universidad de Santiago de Chile, Obispo Umaña 050, Estación Central, Santiago 9160019, Chile.
Escuela de Psicología, Facultad de Ciencias Sociales, Universidad Bernardo O'Higgins, Santiago 8370993, Chile.
Int J Mol Sci. 2022 Jun 13;23(12):6602. doi: 10.3390/ijms23126602.
The misuse of psychostimulants is an increasing behavior among young people, highlighting in some countries the abuse of modafinil (MOD) as a neuropotentiator. However, several clinical trials are investigating MOD as an alternative pharmacological treatment for attentional deficit and hyperactivity disorder (ADHD) in children and adolescents. On the other hand, the early use of psychostimulants and the misdiagnosis rates in ADHD make it crucial to investigate the brain effects of this type of drug in young healthy individuals. The aim of this work was to evaluate the effects of chronic MOD treatment on neurochemicals (γ-aminobutyric acid and glutamate), dopamine receptor 2 (D) expression and behavior (non-selective attention "NSA") in the mesocorticolimbic system of young healthy Sprague-Dawley rats. Preadolescent male rats were injected with MOD (75 mg/kg, i.p.) or a vehicle for 14 days (from postnatal day 22 to 35). At postnatal day 36, we measured the GLU and GABA contents and their extracellular levels in the nucleus accumbens (NAc). In addition, the GLU and GABA contents were measured in the ventral tegmental area (VTA) and D protein levels in the prefrontal cortex (PFC). Chronic use of MOD during adolescence induces behavioral and neurochemical changes associated with the mesocorticolimbic system, such as a reduction in PFC D expression, VTA GABA levels and NSA. These results contribute to the understanding of the neurological effects of chronic MOD use on a young healthy brain.
年轻人中滥用精神兴奋剂的行为日益增多,一些国家突出表现为莫达非尼(MOD)作为神经增强剂的滥用。然而,几项临床试验正在研究 MOD 作为儿童和青少年注意力缺陷多动障碍(ADHD)的替代药物治疗。另一方面,ADHD 中精神兴奋剂的早期使用和误诊率使得调查此类药物对年轻健康个体大脑的影响变得至关重要。本研究旨在评估慢性 MOD 治疗对年轻健康 Sprague-Dawley 大鼠中脑皮质边缘系统神经化学物质(γ-氨基丁酸和谷氨酸)、多巴胺受体 2(D)表达和行为(非选择性注意“NSA”)的影响。在青春期前雄性大鼠中,腹腔注射 MOD(75mg/kg)或载体(22 日龄至 35 日龄),持续 14 天。在出生后第 36 天,我们测量了伏隔核(NAc)中的 GLU 和 GABA 含量及其细胞外水平。此外,还测量了腹侧被盖区(VTA)中的 GLU 和 GABA 含量以及前额叶皮层(PFC)中的 D 蛋白水平。青春期慢性使用 MOD 会引起与中脑皮质边缘系统相关的行为和神经化学变化,例如 PFC D 表达、VTA GABA 水平和 NSA 降低。这些结果有助于理解慢性 MOD 使用对年轻健康大脑的神经影响。