Introduction: Behavioral sensitization is a phenomenon that develops from intermittent exposure to nicotine and other psychostimulants, which often leads to heightened locomotor activity and then relapse. Sulfonamides that act as carbonic anhydrase inhibitors have a documented role in enhancing dopaminergic tone and normalizing neuroplasticity by stabilizing glutamate release.
Objective: The aim of the current study was to explore synthetic sulfonamides derivative 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS) (with documented carbonic anhydrase inhibitory activity) on acquisition and expression of nicotine-induced behavioral sensitization.
Methods: In the acquisition phase, selected 5 groups of mice were exposed to saline or nicotine 0.5mg/kg intraperitoneal (i.p) for 7 consecutive days. Selected 3 groups were administered with 4-FBS 20, 40, and 60 mg/kg p.o. along with nicotine. After 3 days of the drug-free period, ie, day 11, a challenge dose of nicotine was injected to all groups except saline and locomotor activity was recorded for 30 minutes. In the expression phase, mice were exposed to saline and nicotine only 0.5 mg/kg i.p for 7 consecutive days. After 3 days of the drug-free period, ie, day 11, 4-FBS at 20, 40, and 60 mg/kg were administered to the selected groups, one hour after drug a nicotine challenge dose was administered, and locomotion was recorded. At the end of behavioral experiments, all animals were decapitated and the striatum was excised and screened for changes in adenosine levels, using HPLC-UV.
Results: Taken together, our findings showed that 4-FBS in all 3 doses, in both sets of experiments significantly attenuated nicotine-induced behavioral sensitization in mice. Additionally, 4-FBS at 60mg/kg significantly lowered the adenosine level in the striatum.
Conclusion: The behavioral and adenosine modulation is promising, and more receptors level studies are warranted to explore the exact mechanism of action of 4-FBS.

Keywords: 4-fluoro-N-(4-sulfamoylbenzyl) benzene-sulfonamide (4-FBS), nicotine sensitization, pharmacotherapy, drug addiction, locomotor activity, adenosine, HPLC


中文翻译：

---

4-氟-N-(4-磺胺酰基苄基)苯磺酰胺对尼古丁诱导的行为敏化和纹状体腺苷水平的获得和表达的影响

简介：行为致敏是一种由间歇性接触尼古丁和其他精神兴奋剂发展而来的现象，通常会导致运动活动增强，然后复发。作为碳酸酐酶抑制剂的磺胺类药物在通过稳定谷氨酸释放来增强多巴胺能张力和使神经可塑性正常化方面具有文献记载的作用。
目的：本研究的目的是探讨合成磺酰胺衍生物 4-氟-N-(4-氨磺酰基苄基)苯磺酰胺 (4-FBS)（具有记录的碳酸酐酶抑制活性）对尼古丁诱导的行为的获取和表达敏化。
方法：在采集阶段，选择的 5 组小鼠连续 7 天暴露于盐水或 0.5mg/kg 尼古丁腹膜内 (ip)。选择的 3 组与尼古丁一起口服 4-FBS 20、40 和 60 mg/kg。在禁药期3天后，即第11天，向除盐水外的所有组注射激发剂量的尼古丁，并记录运动活动30分钟。在表达阶段，小鼠连续 7 天暴露于盐水和仅 0.5 mg/kg ip 的尼古丁。在停药期 3 天后，即第 11 天，向选定组施用 20、40 和 60 mg/kg 的 4-FBS，在药物后一小时施用尼古丁激发剂量，并记录运动. 在行为实验结束时，
结果：综上所述，我们的研究结果表明，在两组实验中，所有 3 种剂量的 4-FBS 均显着减弱了尼古丁诱导的小鼠行为致敏性。此外，60mg/kg 的 4-FBS 显着降低了纹状体中的腺苷水平。
结论：行为和腺苷调节是有前景的，需要更多的受体水平研究来探索 4-FBS 的确切作用机制。

关键词： 4-氟-N-（4-氨磺酰基苄基）苯磺酰胺（4-FBS），尼古丁致敏，药物治疗，药物成瘾，运动活性，腺苷，HPLC