title: Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats.
abstract: Dipeptidyl-peptidase IV (DPP-IV) is an enzyme responsible for the metabolism of endogenous gut-derived hormone, glucagon-like peptide-1 (GLP-1). DPP-IV is known for its role in energy homeostasis and pharmacological blockade of this enzyme is a recently approved clinical strategy for the management of type II diabetes. Accumulating evidences suggest that enzyme DPP-IV can affect spectrum of central nervous system (CNS) functions. However, little is known about the role of this enzyme in ethanol-mediated neurobehavioral complications. The objective of the present study was to examine the impact of DPP-IV inhibitor, sitagliptin on the development of tolerance to anxiolytic effect of ethanol and anxiety associated with ethanol withdrawal in rats. A dose-response study revealed that sitaglitpin (20 mg/kg, p.o.) per se exhibit anxiolytic effect in the elevated plus maze (EPM) test in rats. Tolerance to anxiolytic effect of ethanol (2 g/kg, i.p.; 8 % w/v) was observed from 7(th) day of ethanol-diet (6 % v/v) consumption. In contrast, tolerance to anxiolytic effect of ethanol was delayed in rats that were treated daily with sitagliptin (20 mg/kg, p.o.) as tolerance was observed from 13(th)day since commencement of ethanol-diet consumption. Discontinuation of rats from ethanol-diet after 15-days of ethanol consumption resulted in withdrawal anxiety between 8 h and 12 h post-abstinence. However, rats on 15-day ethanol-diet with concomitant sitagliptin (20 mg/kg, p.o.) treatment exhibited delay in appearance (24 h post-withdrawal) of withdrawal anxiety. In summary, DPP-IV inhibitors may prove as an attractive research strategy against ethanol tolerance and dependence.
authors.affiliation: Department of Pharmacology, S.T.E.S.s Smt. Kashibai Navale College of Pharmacy, Kondhwa (Bk), Pune, MS, 411048, India, Ajay.Kumar.N.Sharma@uth.tmc.edu.
authors.forename: Ajaykumar N
authors.initials: AN
authors.lastname: Sharma
authors.forename: Ashish
authors.initials: A
authors.lastname: Pise
authors.forename: Jay N
authors.initials: JN
authors.lastname: Sharma
authors.forename: Praveen
authors.initials: P
authors.lastname: Shukla
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000627:therapeutic use*; D001007:Anxiety / Q000188:drug therapy* / Q000209:etiology / Q000523:psychology; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000627:therapeutic use*; D004361:Drug Tolerance / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013375:Substance Withdrawal Syndrome / Q000150:complications / Q000188:drug therapy* / Q000523:psychology
chemical_list: D014151:Anti-Anxiety Agents; D054873:Dipeptidyl-Peptidase IV Inhibitors; D000431:Ethanol