The role of linagliptin, a selective dipeptidyl peptidase-4 inhibitor, in the morphine rewarding effects in rats

Neurochem Int. 2020 Feb:133:104616. doi: 10.1016/j.neuint.2019.104616. Epub 2019 Dec 3.

Abstract

Linagliptin is a selective dipeptidyl peptidase-4 (DPP-4) inhibitor which suppresses the rapid degradation of endogenous glucagon-like peptide-1 (GLP-1). In clinical practice, it is used as an antidiabetic drug, but recent studies have confirmed its role in the activity of the central nervous system (CNS). The reported study focused on the role of linagliptin (10 and 20 mg/kg, ip) in the morphine rewarding effect, analyzing how the agent had influenced the conditioned place preference (CPP) in rats via the expression, acquisition, extinction and reinstatement of the morphine rewarding effect. The obtained results clearly demonstrated linagliptin to inhibit the expression and acquisition, to accelerate the extinction and, eventually, to reduce the reinstatement of morphine-induced CPP. The undertaken experiments significantly extended our knowledge on the mechanisms behind the morphine rewarding effect.

Keywords: Conditioned place preference test; Dipeptidyl peptidase-4; Glucagon-like peptide-1; Linagliptin; Morphine; Rewarding effect.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dipeptidyl Peptidase 4 / drug effects
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Glucagon-Like Peptide 1 / metabolism
  • Hypoglycemic Agents / pharmacology
  • Linagliptin / pharmacology*
  • Male
  • Morphine / pharmacology*
  • Rats, Wistar
  • Reward*

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Hypoglycemic Agents
  • Linagliptin
  • Morphine
  • Glucagon-Like Peptide 1
  • Dipeptidyl Peptidase 4