University of Wollongong
Browse

Liraglutide prevents metabolic side-effects and improves recognition and working memory during antipsychotic treatment in rats

Download (567.2 kB)
journal contribution
posted on 2024-11-15, 01:19 authored by Ilijana Babic, Ashleigh Gorak, Martin Engel, Dominic Sellers, Paul ElsePaul Else, Ashleigh Osborne, Nagesh PaiNagesh Pai, Xu-Feng HuangXu-Feng Huang, Jessica NealonJessica Nealon, Katrina GreenKatrina Green
BACKGROUND: Antipsychotic drugs (APDs), olanzapine and clozapine, do not effectively address the cognitive symptoms of schizophrenia and can cause serious metabolic side-effects. Liraglutide is a synthetic glucagon-like peptide-1 (GLP-1) receptor agonist with anti-obesity and neuroprotective properties. The aim of this study was to examine whether liraglutide prevents weight gain/hyperglycaemia side-effects and cognitive deficits when co-administered from the commencement of olanzapine and clozapine treatment. METHODS: Rats were administered olanzapine (2 mg/kg, three times daily (t.i.d.)), clozapine (12 mg/kg, t.i.d.), liraglutide (0.2 mg/kg, twice daily (b.i.d.)), olanzapine + liraglutide co-treatment, clozapine + liraglutide co-treatment or vehicle (Control) ( n = 12/group, 6 weeks). Recognition and working memory were examined using Novel Object Recognition (NOR) and T-Maze tests. Body weight, food intake, adiposity, locomotor activity and glucose tolerance were examined. RESULTS: Liraglutide co-treatment prevented olanzapine- and clozapine-induced reductions in the NOR test discrimination ratio ( p < 0.001). Olanzapine, but not clozapine, reduced correct entries in the T-Maze test ( p < 0.05 versus Control) while liraglutide prevented this deficit. Liraglutide reduced olanzapine-induced weight gain and adiposity. Olanzapine significantly decreased voluntary locomotor activity and liraglutide co-treatment partially reversed this effect. Liraglutide improved clozapine-induced glucose intolerance. CONCLUSION: Liraglutide co-treatment improved aspects of cognition, prevented obesity side-effects of olanzapine, and the hyperglycaemia caused by clozapine, when administered from the start of APD treatment. The results demonstrate a potential treatment for individuals at a high risk of experiencing adverse effects of APDs

History

Citation

Babic, I., Gorak, A., Engel, M., Sellers, D., Else, P., Osborne, A. L., Pai, N., Huang, X., Nealon, J. & Weston-Green, K. (2018). Liraglutide prevents metabolic side-effects and improves recognition and working memory during antipsychotic treatment in rats. Journal of Psychopharmacology, 32 (5), 578-590.

Journal title

Journal of Psychopharmacology

Volume

32

Issue

5

Pagination

578-590

Language

English

RIS ID

129716

Usage metrics

    Categories

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC