Influence of inhibitors of dipeptidyl peptidase-4 (DPP-4) on naloxone-induced morphine withdrawal signs in rats

• Autorzy: Listos J. , Lupina M. , Talarek S. , Mazur A. , Kotlinska J.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Inhibitors of dipeptidyl peptidase-4 (DPP-4), named as gliptins, are a class of oral antihyperglycemic drugs. They block enzyme – DPP-4, elevating glucagon-like peptide-1 (GLP-1) level. Commonly DPP-4 inhibitors are used to treat diabetes mellitus. An increasing number of data demonstrate that GLP-1 acts as neuropeptide in brain. The exact mechanism of GLP-1 in brain is unclear. It has been demonstrated, that GLP-1 is bound to presynaptic receptors on glutamatergic terminals facilitating glutamate release, without triggering direct postsynaptic effects. GLP-1 is involved in food intake and GLP-1 receptors are located in mesolimbic structures so it is possible that GLP-1 modulators may be involved in addiction. AIM(S): In the present experiment the influence of DPP-4 inhibitor, linagliptin, on morphine withdrawal signs was studied in rats. METHOD(S): Morphine dependence in rats was obtained by administration of increasing doses of morphine, for 8 days. On the 9th day, the subsequent dose of morphine was injected. 1 hour later, naloxone was administered for induction of morphine withdrawal signs in rats. Then, animals were placed into cylinders and number of jumpings was recorded. In order to evaluate the influence of GLP-1 on the expression of morphine withdrawal signs, linagliptin (10 and 20 mg/kg) was administered in rats on the 9th day of the experiment, before the morphine dose. In order to assess the effect of GLP-1 on the acquisition of morphine withdrawal signs, linagliptin (10 and 20 mg/kg) was injected once a day for 8 consecutive days, before morphine injection. RESULTS: In the present study we demonstrated that linagliptin significantly and dose-dependently reduced the expression of morphine withdrawal signs in rats, and only higher dose of linagliptin markedly reduced the acquisition of morphine withdrawal signs in animals. CONCLUSIONS: The present study provides that DPP-4 inhibitor, linagliptin, may be considered as a valuable tool in searching for new strategies in therapy of morphine dependence. FINANCIAL SUPPORT: The study was financed by funds of Medical University of Lublin.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.69

Twórcy

autor

Listos J.

• Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Medical Analytics Division, Medical University Of Lublin, Lublin, Poland

autor

Lupina M.

• Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Medical Analytics Division, Medical University Of Lublin, Lublin, Poland

autor

Talarek S.

• Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Medical Analytics Division, Medical University Of Lublin, Lublin, Poland

autor

Mazur A.

• Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Medical Analytics Division, Medical University Of Lublin, Lublin, Poland

autor

Kotlinska J.

• Department of Pharmacology and Pharmacodynamics, Faculty of Pharmacy with Medical Analytics Division, Medical University Of Lublin, Lublin, Poland