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Article

Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal

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Department of Pharmacology and Pharmacodynamics, Medical University of Lublin, Chodźki 4a St., 20-093 Lublin, Poland
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Department of Pathomorphology and Forensic Medicine, Faculty of Veterinary Medicine, University of Life Sciences, Głęboka 30 St., 20-612 Lublin, Poland
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Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Powstańców Wlkp. 72 Av., 70-111 Szczecin, Poland
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Chair and Department of Experimental and Clinical Pharmacology, Medical University of Lublin, Jaczewskiego 8b St., 20-090 Lublin, Poland
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Experimental Medicine Center, Medical University of Lublin, Jaczewskiego 8d St., 20-090 Lublin, Poland
*
Author to whom correspondence should be addressed.
Academic Editors: Katalin Prokai-Tatrai and Mariana Spetea
Molecules 2022, 27(8), 2478; https://doi.org/10.3390/molecules27082478
Received: 31 January 2022 / Revised: 18 March 2022 / Accepted: 11 April 2022 / Published: 12 April 2022
(This article belongs to the Special Issue Novel Compounds in the Treatment of the CNS Disorders)
(1) Background: Recent data indicate that receptors for GLP-1 peptide are involved in the activity of the mesolimbic system. Thus, the purpose of the present study was to examine the effect of the selective dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, on morphine dependence in mice. (2) Methods: Morphine dependence in mice was obtained by administration of increasing doses of morphine for eight consecutive days, twice a day. On the 9th day of the experiment, the naloxone-induced (2 mg/kg, ip) morphine withdrawal signs (jumping) were assessed. Moreover, behavioral effects of short-term (60 h after morphine discontinuation) and long-term (14 days after morphine discontinuation) morphine withdrawal were observed. In terms of behavioral effects, the depressive effect in the forced swim test and anxiety in the elevated plus maze test were investigated. Locomotor activity of mice was also studied. (3) Results: The administration of linagliptin (10 and 20 mg/kg, ip) for 8 consecutive days before morphine injections significantly diminished the number of naloxone-induced morphine withdrawal signs (jumping) in mice. In addition, the cessation of morphine administration induced depressive behavior in mice which were observed during short- and long-term morphine withdrawal. Linagliptin administered during morphine withdrawal significantly reduced the depressive behavior in studied mice. Furthermore, the short-term morphine withdrawal evoked anxiety which also was reduced by linagliptin in mice. (4) Conclusions: The present study reveals that GLP-1 receptors are involved in morphine dependence. What is more, linagliptin might be a valuable drug in attenuating the physical symptoms of morphine dependence. It might be also a useful drug in reducing emotional disturbances which may develop during the morphine withdrawal period. View Full-Text
Keywords: morphine dependence; glucagon-like peptide-1; dipeptidyl peptidase-4 (DPP-4) inhibitor; morphine withdrawal; the forced swim test; the elevated plus maze test morphine dependence; glucagon-like peptide-1; dipeptidyl peptidase-4 (DPP-4) inhibitor; morphine withdrawal; the forced swim test; the elevated plus maze test
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MDPI and ACS Style

Listos, J.; Listos, P.; Baranowska-Bosiacka, I.; Karpiuk, A.; Filarowska, J.; Łupina, M.; Słowik, T.; Zawiślak, S.; Kotlińska, J. Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal. Molecules 2022, 27, 2478. https://doi.org/10.3390/molecules27082478

AMA Style

Listos J, Listos P, Baranowska-Bosiacka I, Karpiuk A, Filarowska J, Łupina M, Słowik T, Zawiślak S, Kotlińska J. Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal. Molecules. 2022; 27(8):2478. https://doi.org/10.3390/molecules27082478

Chicago/Turabian Style

Listos, Joanna, Piotr Listos, Irena Baranowska-Bosiacka, Agata Karpiuk, Joanna Filarowska, Małgorzata Łupina, Tymoteusz Słowik, Sylwia Zawiślak, and Jolanta Kotlińska. 2022. "Linagliptin, a Selective Dipeptidyl Peptidase-4 Inhibitor, Reduces Physical and Behavioral Effects of Morphine Withdrawal" Molecules 27, no. 8: 2478. https://doi.org/10.3390/molecules27082478

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