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

Abstract

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 heroinseeking. 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. Behavioural Pharmacology 33: 364-376

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration’s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

“…Indeed, GLP-1 analogues may reduce the rewarding effects of palatable food intake (for a review, see also [ 59 ]) and the food-related brain responses in both T2DM and obese subjects in insula, amygdala, putamen, and orbitofrontal cortex [ 62 ]. Consistent with these observations, GLP-1 RA can reduce cue- and drug-induced fentanyl seeking [ 63 ]; physical and behavioral effects of morphine withdrawal [ 58 ]; cue-, stress-, and drug-induced heroin seeking [ 64 ]; and use of cocaine, amphetamine, alcohol, and nicotine in animals when administered over several days or weeks [ 64 , 65 , 66 , 67 ]. In one randomized-controlled trial, exenatide, administered weekly in combination with nicotine replacement therapy, improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers [ 68 ].…”

Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset

“…Indeed, GLP-1 analogues may reduce the rewarding effects of palatable food intake (for a review, see also [59]) and the food-related brain responses in both T2DM and obese subjects in insula, amygdala, putamen, and orbitofrontal cortex [62]. Consistent with these observations, GLP-1RA can reduce: cue-and drug-induced fentanyl seeking [63]; physical and behavioural effects of morphine withdrawal [58]; cue-, stress-, and drug-induced heroin-seeking [64]; use of cocaine, amphetamine, alcohol, and nicotine in animals when administered over several days or weeks [64][65][66][67]. In one randomized-controlled trial, exenatide, administered weekly in combination with nicotine replacement therapy, improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers [68].…”

Is there a risk for Semaglutide Misuse? Focus on the Food and Drug Administration-FDA Adverse Events Reporting System (FAERS) pharmacovigilance dataset

“…Indeed, GLP-1 analogues may reduce the rewarding effects of palatable food intake (for a review, see also [59]) and the food-related brain responses in both T2DM and obese subjects in insula, amygdala, putamen, and orbitofrontal cortex [62]. Consistent with these observations, GLP-1 RA can reduce cueand drug-induced fentanyl seeking [63]; physical and behavioral effects of morphine withdrawal [58]; cue-, stress-, and drug-induced heroin seeking [64]; and use of cocaine, amphetamine, alcohol, and nicotine in animals when administered over several days or weeks [64][65][66][67]. In one randomized-controlled trial, exenatide, administered weekly in combination with nicotine replacement therapy, improved smoking abstinence, reduced craving and withdrawal symptoms, and decreased weight gain among abstainers [68].…”