Taking into account that the neuroinflammation is also considered as one of the pathomechanisms of depression [59], it may be suggested that the beneficial effect of linagliptin on depressive behavior observed in the present study could be associated with GLP-1-induced attenuation of glutamatergic activity and inhibition of neuroinflammatory processes during morphine withdrawal. Here, GLP1R is linked to major depressive disorder.