Chaves Yane Costa, Genaro Karina, Stern Cristina Aparecida, de Oliveira Guaita Gisele, de Souza Crippa José Alexandre, da Cunha Joice Maria, Zanoveli Janaína Menezes
Department of Pharmacology, Biological Science Sector, Federal University of Paraná, Curitiba, Paraná, Brazil.
Institute of Neurosciences and Behavior (INeC), University of Sao Paulo, Ribeirao Preto, Sao Paulo, Brazil; Department of Pharmaceutical Sciences, University of California, Irvine, CA, United States.
Neurosci Lett. 2020 Jun 11;729:135020. doi: 10.1016/j.neulet.2020.135020. Epub 2020 May 1.
The prevalence rates of depression and anxiety are at least two times higher in diabetic patients, increasing morbidity and mortality. Cannabidiol (CBD) has been identified as a therapeutic agent viable to treat diverse psychiatric disorders. Thus, this study aimed to investigate the effect of CBD treatment (once a day for 14 days starting two weeks after diabetes induction; at doses of 0, 3, 10 or 30 mg/kg, i.p.) on depression- and anxiety-like behaviors associated with experimental diabetes induced by streptozotocin (60 mg/kg; i.p.) in rats. Levels of plasma insulin, blood glucose, and weight gain were evaluated in all experimental groups, including a positive control group treated with imipramine. The rats were tested in the modified forced swimming test (mFST) and elevated plus maze (EPM) test. Besides, the levels of serotonin (5-HT), noradrenaline (NA) and dopamine (DA) in two emotion-related brain regions, the prefrontal cortex (PFC) and hippocampus (HIP) were evaluated using high-pressure liquid chromatography. Our results showed that CBD treatment (only at the higher dose of 30 mg/kg) reduced the exaggerated depressive- and anxiogenic-like behaviors of diabetic (DBT) rats, which may be associated with altered 5-HT, NA and/or DA levels observed in the PFC and HIP. Treatment with CBD (higher dose) also induced a significant increase in weight gain and the insulin levels (and consequently reduced glycemia) in DBT rats. The long-term CBD effects gave rise to novel therapeutic strategies to limit the physiological and neurobehavioral deficits in DBT rats. This approach provided evidence that CBD can be useful for treating psychiatry comorbidities in diabetic patients.
糖尿病患者中抑郁症和焦虑症的患病率至少高出两倍,这增加了发病率和死亡率。大麻二酚(CBD)已被确定为一种可用于治疗多种精神疾病的治疗剂。因此,本研究旨在调查CBD治疗(在糖尿病诱导两周后开始,每天一次,持续14天;腹腔注射剂量为0、3、10或30mg/kg)对链脲佐菌素(60mg/kg;腹腔注射)诱导的实验性糖尿病大鼠相关的抑郁样和焦虑样行为的影响。在所有实验组中评估血浆胰岛素水平、血糖水平和体重增加情况,包括用丙咪嗪治疗的阳性对照组。对大鼠进行改良强迫游泳试验(mFST)和高架十字迷宫(EPM)试验。此外,使用高压液相色谱法评估两个与情绪相关的脑区,前额叶皮质(PFC)和海马体(HIP)中的血清素(5-HT)、去甲肾上腺素(NA)和多巴胺(DA)水平。我们的结果表明,CBD治疗(仅在较高剂量30mg/kg时)减少了糖尿病(DBT)大鼠过度的抑郁样和焦虑样行为,这可能与在PFC和HIP中观察到的5-HT、NA和/或DA水平的改变有关。CBD(较高剂量)治疗还导致DBT大鼠体重增加和胰岛素水平显著升高(从而降低血糖)。CBD的长期作用产生了限制DBT大鼠生理和神经行为缺陷 的新治疗策略。这种方法提供了证据,证明CBD可用于治疗糖尿病患者的精神共病。