Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats

利拉鲁肽 海洛因 医学 药品 药理学 尼古丁 自我管理 类阿片 药物滥用 兴奋剂 上瘾 育亨宾 内科学 糖尿病 受体 内分泌学 精神科 2型糖尿病 敌手
作者
Joaquin E. Douton,Nikhil Acharya,Brooke Stoltzfus,Dongxiao Sun,Patricia S. Grigson,Jennifer E. Nyland
出处
期刊:Behavioural Pharmacology [Lippincott Williams & Wilkins]
卷期号:33 (5): 364-378 被引量:8
标识
DOI:10.1097/fbp.0000000000000685
摘要

Substance use disorder is challenging to treat due to its relapsing nature. In the last decade, opioid use disorder has been a threat to public health, being declared an epidemic by the Centers for Disease Control and Prevention. This is a tragic situation, considering there currently are only three effective, yet not ideal, treatments to prevent relapse to opioids. Recent research has shown that hormones that modulate hunger and satiety also can modulate motivated behavior for drugs of abuse. For example, the short-acting analog of glucagon-like peptide-1 (GLP-1), an incretin hormone that regulates homeostatic feeding, has been shown to reduce responding for rewarding stimuli such as food, cocaine, heroin, and nicotine when administered over several days or weeks. This may serve as an effective adjuvant during treatment; however, whether it would be effective when used acutely to bridge a patient between cessation of use and onset of medication for the treatment of an opioid addiction is unknown. Here, we tested the acute effects of the longer acting GLP-1 analog, liraglutide, on heroin-seeking. In rats with heroin self-administration experience, we found that subcutaneous administration of an acute dose of 0.3-mg/kg liraglutide was effective in preventing drug-seeking after exposure to three major precipitators: drug-associated cues, stress (yohimbine-induced), and the drug itself. Finally, we confirmed that the reduction in drug-seeking is not due to a locomotor impairment, as liraglutide did not significantly alter performance in a rotarod test. As such, acute use of GLP-1 analogs may serve as a new and effective nonopioid bridge to treatment.
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