服用羟考酮会阻止催产素降低大鼠的酒精摄入量。

IF 2.5 4区医学 Q3 PHARMACOLOGY & PHARMACY

Alcohol Pub Date : 2025-02-01 DOI:10.1016/j.alcohol.2024.10.002

C.S. Wilkinson , C.G. Modrak , T.D. Thompson , R.C. Conrad , I. Leon , L.A. Knackstedt

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引用次数: 0

摘要

酒精和阿片类药物的多重使用（PSU）很常见，而且往往伴随着较高的特质焦虑。催产素可降低焦虑、酒精和阿片类药物的寻求和摄取，但尚未在 PSU 的背景下进行过评估。在此，我们建立了一个连续服用羟考酮和酒精的 PSU 大鼠模型，以研究焦虑、酒精和羟考酮摄入量之间的关系，以及全身性催产素对减少酒精摄入量的功效。使用声惊吓和高架加迷宫（EPM）对雌雄 Sprague-Dawley 大鼠进行基线焦虑样行为评估。然后让大鼠连续 7 天每天 6 小时两瓶地选择使用羟考酮和/或水，然后再连续 10 天每天 24 小时五瓶地选择使用酒精（20% v/v）和/或水。接下来，单物质（羟考酮或酒精）大鼠继续每天只接触一种物质，而 PSU 大鼠则接触羟考酮和水 3 小时，然后接触酒精和水 6 小时。12 天后，大鼠在接触酒精 20 小时后接受 EPM 测试，以检查戒断相关焦虑。然后，在大鼠服用羟考酮/水后，即饮酒前 30 分钟给大鼠注射催产素（0、0.3 或 1.0 mg/kg IP）。大鼠先胃内注射羟考酮（2 毫克/千克）或水，然后胃内注射酒精（2 克/千克），并采血测定血液中的酒精含量。基线焦虑样行为的增加伴随着酒精摄入量的减少。服用羟考酮不会改变酒精摄入量，但会减少戒断时的焦虑样行为，并阻止催产素减少酒精摄入量。催产素（1 毫克/千克）可减少纯酒精条件下的酒精摄入量，这种效果在注射一次催产素后可持续数天。在无酒精条件下接受催产素治疗的大鼠比未接受治疗的大鼠显示出更高的血液酒精浓度。这些结果支持了在 PSU 啮齿动物模型中测试药物使用的必要性。

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Consumption of oxycodone prevents oxytocin from attenuating alcohol intake in rats

Alcohol and opioid polysubstance use (PSU) is common and often accompanied by higher trait anxiety. Oxytocin decreases anxiety, alcohol- and opioid-seeking and -taking but has not been assessed in the context of PSU. Here we developed a rat model of sequential oxycodone and alcohol PSU to examine the relationship between anxiety, alcohol and oxycodone intake, and the efficacy of systemic oxytocin to attenuate alcohol intake. Male and female Sprague–Dawley rats were assessed for baseline anxiety-like behavior using acoustic startle and the elevated plus maze (EPM). Rats were then given 2-bottle choice access to oxycodone and/or water for 6-hr/day for 7 days, followed by 2-bottle choice access to alcohol (20% v/v) and/or water for five 24-hr sessions across 10 days. Next, monosubstance (oxycodone- or alcohol-alone) rats continued to have access to only one substance/day while PSU rats had access to oxycodone and water for 3-hr, followed by alcohol and water for 6-hr. After 12 days, rats were tested in the EPM 20 h after alcohol access to examine withdrawal-related anxiety. Next, oxytocin (0, 0.3 or 1.0 mg/kg IP) was administered following the oxycodone/water session, 30 min prior to alcohol access. Rats received intragastric oxycodone (2 mg/kg) or water followed by intragastric alcohol (2 g/kg) and blood was collected to determine blood alcohol levels. Elevated baseline anxiety-like behavior was accompanied by reduced alcohol intake. Consumption of oxycodone did not alter alcohol intake but resulted in less anxiety-like behavior during withdrawal and prevented oxytocin from attenuating alcohol intake. Oxytocin (1 mg/kg) reduced alcohol intake in the alcohol-only condition, an effect that persisted for days after a single oxytocin administration. Rats that received oxycodone prior to non-contingent alcohol displayed higher blood alcohol levels than those that did not. These results support the necessity for the testing of medications for substance use in rodent models of PSU.

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来源期刊

Alcohol 医学-毒理学

CiteScore

4.60

自引率

4.30%

发文量

审稿时长

15.6 weeks

期刊介绍： Alcohol is an international, peer-reviewed journal that is devoted to publishing multi-disciplinary biomedical research on all aspects of the actions or effects of alcohol on the nervous system or on other organ systems. Emphasis is given to studies into the causes and consequences of alcohol abuse and alcoholism, and biomedical aspects of diagnosis, etiology, treatment or prevention of alcohol-related health effects. Intended for both research scientists and practicing clinicians, the journal publishes original research on the neurobiological, neurobehavioral, and pathophysiological processes associated with alcohol drinking, alcohol abuse, alcohol-seeking behavior, tolerance, dependence, withdrawal, protracted abstinence, and relapse. In addition, the journal reports studies on the effects alcohol on brain mechanisms of neuroplasticity over the life span, biological factors associated with adolescent alcohol abuse, pharmacotherapeutic strategies in the treatment of alcoholism, biological and biochemical markers of alcohol abuse and alcoholism, pathological effects of uncontrolled drinking, biomedical and molecular factors in the effects on liver, immune system, and other organ systems, and biomedical aspects of fetal alcohol spectrum disorder including mechanisms of damage, diagnosis and early detection, treatment, and prevention. Articles are published from all levels of biomedical inquiry, including the following: molecular and cellular studies of alcohol''s actions in vitro and in vivo; animal model studies of genetic, pharmacological, behavioral, developmental or pathophysiological aspects of alcohol; human studies of genetic, behavioral, cognitive, neuroimaging, or pathological aspects of alcohol drinking; clinical studies of diagnosis (including dual diagnosis), treatment, prevention, and epidemiology. The journal will publish 9 issues per year; the accepted abbreviation for Alcohol for bibliographic citation is Alcohol.