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

Journal Article


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Abstract


  • 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

Publication Date


  • 2018

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.

Scopus Eid


  • 2-s2.0-85046421110

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=1127&context=smhpapers1

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/126

Number Of Pages


  • 12

Start Page


  • 578

End Page


  • 590

Volume


  • 32

Issue


  • 5

Place Of Publication


  • United Kingdom

Abstract


  • 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

Publication Date


  • 2018

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.

Scopus Eid


  • 2-s2.0-85046421110

Ro Full-text Url


  • https://ro.uow.edu.au/cgi/viewcontent.cgi?article=1127&context=smhpapers1

Ro Metadata Url


  • http://ro.uow.edu.au/smhpapers1/126

Number Of Pages


  • 12

Start Page


  • 578

End Page


  • 590

Volume


  • 32

Issue


  • 5

Place Of Publication


  • United Kingdom