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A relatively new class of drugs, glucagon-like peptide-1 (GLP-1) receptor agonists, have had much success in the treatment of type 2 diabetes. Now, these drugs may offer support in the treatment of addiction and drug abuse.
A new study, published in Translational Psychiatry, reports that GLP-1 receptors may be a target for treating drug abuse. The study was conducted in mice, but it calls attention to previous reports with similar findings.
Dopamine is essential to reward pathways that influence drug abuse and addiction. Endocannabinoids and arachidonic acid, which are also naturally present in the brain, affect the function of dopamine transporters. Activation of GLP-1 receptors reduces arachidonic acid in areas of the brain that are associated with reward; dopamine levels, in turn, reduce. In the current study, the long-lasting GLP-1 receptor agonist, exenatide, abolished cocaine-induced increases in dopamine levels.
GLP-1 is normally found in the gut and influences satiety signaling. In part, GLP-1 agonists, which mimic the activity of naturally-occurring GLP-1, regulate glucose homeostasis in type 2 diabetes by promoting a feeling of fullness. These drugs have been shown to aid in weight loss in patients with type 2 diabetes. These effects might also be due to the reduction in the rewarding effects of food, owing to GLP-1 action in regulating dopamine transporter activity and reducing reward related to food intake.
Both illicit drugs and palatable foods activate reward pathways in the brain. Therefore, pharmacologic modulation of these central nervous system circuits holds promise for reducing unwanted or abusive behaviors. The role of naturally occurring GLP-1 in affecting reward is unknown. The beneficial effects of GLP-1 agonist activity are now believed to extend not just to food, but alcohol and to psychostimulants, such as cocaine and amphetamine.
Several recent studies have highlighted the mechanism by which GLP-1 agonists influence reward-inducing behaviors in the central nervous system. While the place in therapy is not clearly defined, these findings could expand the therapeutic potential of this entire class of drugs.
Harasta AE, Power JM, von Jonquieres G, et al. Septal glucagon-like peptide 1 receptor expression determines suppression of cocaine-induced behavior (2015) Neuropsychopharmacology, 40(8):1969-78. PMID: 25669605
Reddy IA, Pino JA, Weikop P, et al. Glucagon-like peptide-1 receptor activation regulates cocaine actions and dopamine homeostasis in the lateral septum by decreasing arachidonic acid levels (2016) Transl Psychiatry, 6:e809. PMID: 27187231
Richards JE, Anderberg RH, Goteson, et al. Activation of the GLP-1 receptors in the nucleus of the solitary tract reduces food reward behavior and targets the mesolimbic system (2015) PLoS One, 110(3):e0119034. PMID: 25793511
Sirohi S, Schurdak JD, Seeley RJ, et al. Contral peripheral glucagon-like peptide-1 receptor signaling differentially regulate addictive behaviors (2016) Physiol Behav, 161:140-4. PMID: 27072507
Skibicka KP. The central GLP-1: implications for food and drug reward (2013) Front Neurosci 7:181. PMID: 24133407
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