Rezvani Amir H, Levin Edward D, Cauley Marty, Getachew Bruk, Tizabi Yousef
Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, NC 27710, USA.
Department of Pharmacology, College of Medicine, Howard University, Washington, DC 20059, USA.
J Drug Alcohol Res. 2017;6. doi: 10.4303/jdar/236030. Epub 2017 Jul 28.
Although various pharmacological tools in combating addiction to alcohol are available, their efficacy is limited. Hence, there is a critical need for development of more effective medications. Recent advances in the field have identified the glutamatergic system as a potential novel target for intervention in addictive behaviors.
Hence, we evaluated the effects of acute administration of low (subanesthetic) doses of ketamine, an NMDA receptor antagonist, on alcohol intake and alcohol preference in both male and female rats.
Adult alcohol preferring (P) rats were exposed to two-bottle choice (ethanol 10% and water) for at least three weeks following a nine-day training period and the effects of various doses of ketamine (5 mg/kg, 7.5 mg/kg, and 10 mg/kg, injected subcutaneously, SC) on consumption of alcohol over various time periods during a 24 h interval were measured.
Our results indicate that ketamine treatment significantly reduced both alcohol intake and preference in a time- and dose-dependent manner in both sexes. Moreover, a differential sensitivity between the sexes was observed. Thus, although alcohol intake was higher in males, female rats responded much more strongly to the highest dose of ketamine than males in the initial time periods.
It is concluded that glutamatergic receptor manipulations may be of therapeutic potential in addiction to alcohol and that different sexes may respond differentially to such treatments.
尽管有多种对抗酒精成瘾的药物工具，但它们的疗效有限。因此，迫切需要开发更有效的药物。该领域的最新进展已确定谷氨酸能系统是干预成瘾行为的潜在新靶点。
因此，我们评估了急性给予低（亚麻醉）剂量的氯胺酮（一种NMDA受体拮抗剂）对雄性和雌性大鼠酒精摄入量及酒精偏好的影响。
成年嗜酒（P）大鼠在经过九天的训练期后，接受两瓶选择（10%乙醇和水）至少三周，测量了不同剂量的氯胺酮（5毫克/千克、7.5毫克/千克和10毫克/千克，皮下注射，SC）在24小时间隔内不同时间段对酒精消耗的影响。
我们的结果表明，氯胺酮治疗在两性中均以时间和剂量依赖的方式显著降低了酒精摄入量和偏好。此外，观察到两性之间存在差异敏感性。因此，尽管雄性的酒精摄入量较高，但在最初时间段内，雌性大鼠对最高剂量氯胺酮的反应比雄性强烈得多。
得出的结论是，谷氨酸能受体操纵在酒精成瘾方面可能具有治疗潜力，并且不同性别对这种治疗的反应可能不同。
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