Mortality in psychiatric patients with severe mental illnesses reaches a 2-3 times higher mortality rate compared to the general population, primarily due to somatic comorbidities. A high prevalence of cardiovascular morbidity can be attributed to the adverse metabolic effects of atypical antipsychotics (atypical APs), but also to metabolic dysregulation present in drug-naïve patients. The metabolic aspects of neurodevelopmental schizophrenia-like models are understudied. This study evaluated the metabolic phenotype of a methylazoxymethanol (MAM) schizophrenia-like model together with the metabolic effects of three APs [olanzapine (OLA), risperidone (RIS) and haloperidol (HAL)] administered via long-acting formulations for 8 weeks in female rats. Body weight, feed efficiency, serum lipid profile, gastrointestinal and adipose tissue-derived hormones (leptin, ghrelin, glucagon and glucagon-like peptide 1) were determined. The lipid profile was assessed in APs-naïve MAM and control cohorts of both sexes. Body weight was not altered by the MAM model, though cumulative food intake and feed efficiency was lowered in the MAM compared to CTR animals. The effect of the APs was also present; body weight gain was increased by OLA and RIS, while OLA induced lower weight gain in the MAM rats. Further, the MAM model showed lower abdominal adiposity, while OLA increased it. Serum lipid profile revealed MAM model-induced alterations in both sexes; total, HDL and LDL cholesterol levels were increased. The MAM model did not exert significant alterations in hormonal parameters except for elevation in leptin level. The results support intrinsic metabolic dysregulation in the MAM model in both sexes, but the MAM model did not manifest higher sensitivity to metabolic effects induced by antipsychotic treatment.

Department of Biomedical and Biotechnological Sciences Section of Pharmacology University of Catania Via Santa Sofia 97 1 95123 Catania Italy

Department of Human Pharmacology and Toxicology Faculty of Pharmacy Masaryk University Palackeho trida 1946 1 612 00 Brno Czech Republic

Department of Human Pharmacology and Toxicology Faculty of Pharmacy University of Veterinary and Pharmaceutical Sciences Palackeho trida 1946 1 612 00 Brno Czech Republic

Department of Pharmacology Faculty of Medicine Masaryk University Kamenice 5 62500 Brno Czech Republic

Department of Stress Neurobiology and Neurogenetics Neuronal Plasticity Group Max Planck Institute of Psychiatry Kraepelinstrasse 2 10 80804 Munich Germany

National Institute of Mental Health Topolova 748 250 67 Klecany Czech Republic

R and D Department Biovendor Laboratorni Medicina Karasek 1 621 00 Brno Czech Republic

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