Ashraf Ghulam Md, Alghamdi Badrah S, Alshehri Fahad S, Alam Mohammad Zubair, Tayeb Haythum O, Tarazi Frank I
Pre-Clinical Research Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Front Pharmacol. 2021 Apr 19;12:578716. doi: 10.3389/fphar.2021.578716. eCollection 2021.
Atypical antipsychotic drugs are commonly associated with undesirable side effects including body weight gain (BWG) and metabolic deficits. Many pharmacological interventions have been tested in an attempt to minimize or prevent these side effects. Preliminary evidence suggests that antidiabetic drugs may be effective in attenuating antipsychotic-induced BWG. In the current study, we examined the effect of an antidiabetic drug empagliflozin (EMPA) on BWG induced by anatypical antipsychotic drug olanzapine (Ola) in female and male Wistar rats. Rats were divided into six groups based on the dose they received: group 1 (female control), group 2 (female EMPA, 20 mg/kg; IG), group 3 (female Ola, 4 mg/kg; IP), group 4 (female Ola, 4 mg/kg; IP + EMPA, 20 mg/kg; IG), group 5 (male control), and group 6 (male Ola, 4 mg/kg; IP). Ola induced sustained increase in BWG. The subsequent treatment of Group 3 and 4 with EMPA attenuated the Ola-induced BWG in female Wistar rats. In terms of the gender difference between female and male Wistar rats, the male control group 5 gained more weight throughout the study as compared to the female control group 1. Similarly, the male Ola group 6 gained more weight throughout the study as compared to the female Ola group 3. However, Ola did not cause any weight difference between male rats treated with Ola in comparison with male control group, thus showing a significant gender difference regarding body weight between male and female Wistar rats regardless of Ola administration. In addition, the present findings showed that EMPA effectively attenuates the Ola induced BWG in female Wistar rats. These novel findings should help to better understand the underlying molecular and behavioral mechanisms contributing to the observed increase in body weight after treatment with Ola and other atypical antipsychotic drugs across male and female rats.
非典型抗精神病药物通常会带来包括体重增加（BWG）和代谢缺陷等不良副作用。人们已经测试了许多药理学干预措施，试图将这些副作用降至最低或加以预防。初步证据表明，抗糖尿病药物可能有效减轻抗精神病药物引起的体重增加。在本研究中，我们检测了抗糖尿病药物恩格列净（EMPA）对非典型抗精神病药物奥氮平（Ola）诱导的雌性和雄性Wistar大鼠体重增加的影响。根据大鼠接受的剂量将其分为六组：第1组（雌性对照组），第2组（雌性恩格列净，20mg/kg；灌胃），第3组（雌性奥氮平，4mg/kg；腹腔注射），第4组（雌性奥氮平，4mg/kg；腹腔注射 + 恩格列净，20mg/kg；灌胃），第5组（雄性对照组），第6组（雄性奥氮平，4mg/kg；腹腔注射）。奥氮平导致体重持续增加。第3组和第4组随后用恩格列净治疗，减轻了雌性Wistar大鼠中奥氮平诱导的体重增加。就雌性和雄性Wistar大鼠之间的性别差异而言，在整个研究过程中，雄性对照组第5组比雌性对照组第1组体重增加更多。同样，在整个研究过程中，雄性奥氮平组第6组比雌性奥氮平组第3组体重增加更多。然而，与雄性对照组相比，奥氮平并未使接受奥氮平治疗的雄性大鼠之间出现任何体重差异，因此表明无论是否给予奥氮平，雄性和雌性Wistar大鼠在体重方面存在显著的性别差异。此外，目前的研究结果表明，恩格列净有效地减轻了雌性Wistar大鼠中奥氮平诱导的体重增加。这些新发现应有助于更好地理解在雄性和雌性大鼠中使用奥氮平和其他非典型抗精神病药物治疗后体重增加背后的潜在分子和行为机制。
