Department of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
Department of Pharmacy, College of Pharmacy, Al-Zaytoonah University of Jordan, Amman, Jordan.
Brain Res Bull. 2022 Jul;185:56-63. doi: 10.1016/j.brainresbull.2022.04.014. Epub 2022 Apr 29.
Chronic tobacco exposure can alter the endocannabinoid (eCB) system, consequently leading to an anxiety state. In this study, we investigated the effects of waterpipe tobacco smoke (WTS) on cannabinoid receptor 1 and 2 (CBR1 and CBR2) gene and protein expression in mesocorticolimbic brain regions. Using elevated plus maze (EPM) and open field (OF) tests, the effects of WTS exposure on withdrawal-induced anxiety-like behavior were examined. The effect of ceftriaxone (CEF), a β-lactam known to upregulate glutamate transporter 1 (GLT-1), on anxiety and the expression of cannabinoid receptors was also determined. Male Sprague-Dawley rats were randomly assigned to four groups: 1) the Control group was exposed only to standard room air; 2) the WTS group was exposed to tobacco smoke and treated with saline vehicle; 3) the WTS-CEF group was exposed to WTS and treated with ceftriaxone; and 4) the CEF group was exposed only to standard room air and treated with ceftriaxone. Rats were exposed to WTS (or room air) for two hours per day, five days per week for a period of four weeks. Behavioral tests (EPM and OF) were conducted weekly during acute withdrawal, 24 h following WTS exposure. Rats were given either saline or ceftriaxone (200 mg/kg i.p.) for five days during Week 4, 30 min prior to WTS exposure. Withdrawal-induced anxiety was induced by WTS exposure but was reduced by ceftriaxone treatment. WTS exposure decreased CBR1 mRNA and protein expression in the NAc and VTA, but not PFC, and ceftriaxone treatment attenuated these effects. WTS exposure did not change CBR2 mRNA expression in the NAc, VTA, or PFC. These findings demonstrate that WTS exposure dysregulated the endocannabinoid system and increased anxiety-like behavior, and these effects were reversed by ceftriaxone treatment, which suggest the involvement of glutamate transporter 1 in these effects.
慢性烟草暴露会改变内源性大麻素（eCB）系统，从而导致焦虑状态。在这项研究中，我们研究了水烟烟草烟雾（WTS）对中皮质边缘脑区大麻素受体 1 和 2（CBR1 和 CBR2）基因和蛋白表达的影响。使用高架十字迷宫（EPM）和旷场（OF）测试，研究了 WTS 暴露对戒断诱导的焦虑样行为的影响。还确定了头孢曲松（CEF），一种已知上调谷氨酸转运体 1（GLT-1）的β-内酰胺类药物，对焦虑和大麻素受体表达的影响。雄性 Sprague-Dawley 大鼠被随机分配到四组：1）对照组仅暴露于标准室内空气；2）WTS 组暴露于烟草烟雾并用生理盐水处理；3）WTS-CEF 组暴露于 WTS 并用头孢曲松处理；4）CEF 组仅暴露于标准室内空气并用头孢曲松处理。大鼠每天暴露于 WTS（或室内空气）两小时，每周五天，持续四周。在急性戒断期间每周进行行为测试（EPM 和 OF），WTS 暴露后 24 小时。在第 4 周期间，大鼠每周接受五天盐水或头孢曲松（200mg/kg ip）治疗，在 WTS 暴露前 30 分钟。WTS 暴露引起戒断诱导的焦虑，但头孢曲松治疗减轻了这种作用。WTS 暴露降低了 NAc 和 VTA 中的 CBR1 mRNA 和蛋白表达，但 PFC 中没有，头孢曲松治疗减弱了这些作用。WTS 暴露没有改变 NAc、VTA 或 PFC 中的 CBR2 mRNA 表达。这些发现表明，WTS 暴露使内源性大麻素系统失调并增加焦虑样行为，头孢曲松治疗逆转了这些作用，这表明谷氨酸转运体 1 参与了这些作用。
