Crosstalk Between Glycinergic and N-Methyl-D-Aspartate Receptor-Mediated Glutamatergic Transmission in Behaviours Associated with Opioid Use Disorder.

The current pharmacological approach for the treatment of opioid use disorder (OUD), as a result of prescription misuse or illicit opioids, utilises opioid ligands that have either an agonist or antagonist profile. In this context, methadone and buprenorphine act as opioid agonists, whereas naltrexone functions as an opioid antagonist. To decrease the reinforcing effects of illicit opioids, higher doses of methadone and buprenorphine have been recommended, but this is associated with increased side effects. Therefore, several preclinical efforts have been carried out over the last decades to find drugs that act on receptors other than opioid receptors. A large body of preclinical evidence has shown the ability of N-methyl-D-aspartate receptor (NMDAR) antagonists like ketamine to treat opioid addiction behaviours in animals. Indeed, ketamine by itself is an addictive drug; thus, the treatment of OUD is still a matter to be solved. Growing data position glycine transporter 1 as a possible therapeutic target for the treatment of substance use disorder. This transporter regulates the reuptake of glycine, which can modulate the function of both NMDARs and GPR158, a metabotropic glycine receptor (mGlyR); thus, it is worth investigating in the management of OUD. To gain insight into the role of glycinergic transmission in OUD, alongside NMDAR-mediated glutamatergic transmission, dopaminergic and GABAergic transmission were also reviewed.