Liraglutide prevents metabolic side-effects and improves recognition and working memory during antipsychotic treatment in rats. (May 2018)

• Record Type: Journal Article
• Authors: Babic, Ilijana; Gorak, Ashleigh; Engel, Martin; Sellers, Dominic; Else, Paul; Osborne, Ashleigh L; Pai, Nagesh; Huang, Xu-Feng; Nealon, Jessica; Weston-Green, Katrina
• Is Part Of: Journal of psychopharmacology. Volume 32:Number 5(2018)
• Page Start: 578
• Page End: 590
• Publication Date: 2018-05
• Subjects: Cognition -- glucagon-like peptide-1 -- liraglutide -- antipsychotic -- obesity; Psychopharmacology -- Periodicals; 615.78
• DOI: 10.1177/0269881118756061
• Languages: English
• ISSNs: 0269-8811

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.