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Metabolic Brain Disease

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01.06.2015 | Research Article

Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats

verfasst von: Ajaykumar N. Sharma, Ashish Pise, Jay N. Sharma, Praveen Shukla

Erschienen in: Metabolic Brain Disease | Ausgabe 3/2015

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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^thday 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.

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Titel: Dipeptidyl-peptidase IV (DPP-IV) inhibitor delays tolerance to anxiolytic effect of ethanol and withdrawal-induced anxiety in rats
verfasst von: Ajaykumar N. Sharma
Ashish Pise
Jay N. Sharma
Praveen Shukla
Publikationsdatum: 01.06.2015
Verlag: Springer US
Erschienen in: Metabolic Brain Disease / Ausgabe 3/2015
Print ISSN: 0885-7490
Elektronische ISSN: 1573-7365
DOI: https://doi.org/10.1007/s11011-014-9603-7

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