%0 Journal Article %A Annika Billefeld Bornebusch %A Anders Fink-Jensen %A Gitta Wörtwein %A Randy J. Seeley %A Morgane Thomsen %T Glucagon-Like Peptide-1 receptor agonist treatment does not reduce abuse-related effects of opioid drugs %D 2019 %R 10.1523/ENEURO.0443-18.2019 %J eneuro %P ENEURO.0443-18.2019 %X Dependence on opioids and the number of opioid overdose deaths are serious and escalating public health problems, but medication-assisted treatments for opioid addiction remain inadequate for many patients. Glucagon-like pepide-1 (GLP-1) is a gut hormone and neuropeptide with actions in peripheral tissues and in the brain, including regulation of blood glucose and food intake. GLP-1 analogs, which are approved diabetes medications, can reduce the reinforcing and rewarding effects of alcohol, cocaine, amphetamine, and nicotine in rodents. Investigations on effects of GLP-1 analogs on opioid reward and reinforcement have not been reported. We assessed the effects of the GLP-1 receptor agonist Exendin-4 (Ex4) on opioid-related behaviors in male mice, i.e. morphine-conditioned place preference, intravenous self-administration of the short-acting synthetic opioid remifentanil, naltrexone-precipitated morphine withdrawal, morphine analgesia (male and female mice), and locomotor activity. Ex4 treatment had no effect on morphine-induced conditioned place preference, withdrawal, or hyperlocomotion. Ex4 failed to decrease remifentanil self-administration, if anything reinforcing effects of remifentanil appeared increased in Ex-4 treated mice relative to saline. Ex4 did not significantly affect analgesia. In contrast, Ex4 dose-dependently decreased oral alcohol self-administration, and suppressed spontaneous locomotor activity. Taken together, Ex4 did not attenuate the addiction-related behavioral effects of opioids, indicating that GLP-1 analogs would not be useful medications in the treatment of opioid addiction. This difference between opioids and other drug classes investigated to date may shed light on the mechanism of action of GLP-1 receptor treatment in the addictive effects of alcohol, central stimulants, and nicotine.Significance Statement Opioid overdoses are now the leading cause of death for age under 50 in the USA, and effective new treatments to curb opioid addiction worldwide are urgently needed. GLP-1 analogs are safe, approved, diabetes medications that have shown promising "anti-addiction" effects in preclinical studies with alcohol, central stimulants, and nicotine. In the present study, we report that GLP-1 receptor stimulation does not attenuate rewarding or reinforcing effects of opioid drugs and does not attenuate acquisition or expression of opioid withdrawal. %U https://www.eneuro.org/content/eneuro/early/2019/04/08/ENEURO.0443-18.2019.full.pdf