Furthermore, acute administration of the selective MOR agonists, such as methadone, fentanyl, morphine, hydrocodone, buprenorphine, and nalbuphine in an intracranial self-stimulation (ICSS)blocked both stimulation of stretching and depression produced by lactic acid[39].Recently a novel DOR agonist, KNT-127 demonstrated antidepressant-like and antinociceptive effects in mice without producing convulsions[40]. This evidence concerns the gene OPRM1 and depressive disorder.