Acute Glucagon-Like Peptide-1 Receptor Agonist Liraglutide Prevents Drug-Induced Heroin Seeking in Rats

Abstract

AbstractSubstance use disorder is a difficult disease 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 are currently effective, yet not ideal, treatments to prevent relapse. 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. Here, we tested the acute effects of the long-acting GLP-1 analog, liraglutide, on heroin seeking. We found that, in rats with heroin self-administration experience, subcutaneous (sc) administration of an acute dose of 0.3 mg/kg liraglutide was effective in preventing relapse after exposure to three major precipitators: drug-associated cues, stress, and the drug itself. However, the effects of the drug were contingent upon the pretreatment time, with the drug being fully effective when administered using a 6 h, rather than a 4 h pretreatment time. 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, this acute non-opioid treatment may serve as a new and effective bridge to treatment.