OBJECTIVES: Patients with schizophrenia often suffer comorbid substance abuse regardless of gender. However, the vast majority of studies are only conducted in male subjects. Therefore, the aim of these experiments is to assess addictive behaviors of both sexes in a neurodevelopmental model of schizophrenia induced by prenatal methylazoxymethanol (MAM) acetate exposure. METHODS: MAM (22 mg/kg) was administered intraperitoneally on gestational day 17. Two studies were performed in the offspring: (1) an alcohol-drinking procedure to assess daily intake of 20% alcohol and relapse-like behavior after a period of forced abstinence; (2) Methamphetamine (METH) intravenous self administration (IVSA) followed by forced abstinence and reinstatement phases. RESULTS: MAM exposure during the prenatal period did not change alcohol drinking regardless of sex. However, MAM females showed higher alcohol consumption in comparison to MAM males. The METH IVSA study revealed only a modest increase of drug consumption in MAM males, while there was no difference between the female groups. Reinstatement data showed no effect of the MAM model in either sex, but suggested increased responding in female rats. CONCLUSIONS: This study suggests that female sex and schizophrenia-like phenotype may work synergistically to enhance alcohol consumption. However, future research is needed to establish paradigms in which these findings would be readily assessed to test anti-addiction treatments.

b Department of Biomedical and Biotechnological Sciences Section of Pharmacology School of Medicine University of Catania Catania Italy

c Behavioral and Social Neuroscience Group CEITEC Central European Institute of Technology Masaryk University Brno Czech Republic

Department of Pharmacology Faculty of Medicine Masaryk University Brno Czech Republic

References provided by Crossref.org

Prenatal MAM exposure raises kynurenic acid levels in the prefrontal cortex of adult rats

Olanzapine, but not haloperidol, exerts pronounced acute metabolic effects in the methylazoxymethanol rat model

The Effects of Peripubertal THC Exposure in Neurodevelopmental Rat Models of Psychopathology

The effect of CNQX on self-administration: present in nicotine, absent in methamphetamine model

Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia

Different effects of prenatal MAM vs. perinatal THC exposure on regional cerebral blood perfusion detected by Arterial Spin Labelling MRI in rats

Both ketamine and NBQX attenuate alcohol drinking in male Wistar rats

HDAC1 and HDAC3 underlie dynamic H3K9 acetylation during embryonic neurogenesis and in schizophrenia-like animals

Suppression of Methamphetamine Self-Administration by Ketamine Pre-treatment Is Absent in the Methylazoxymethanol (MAM) Rat Model of Schizophrenia