Reactivity to addictive drugs in the methylazoxymethanol (MAM) model of schizophrenia in male and female rats

Abstract

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.

Keywords:

• Abuse
• alcohol
• methamphetamine
• sex differences
• schizophrenia

Acknowledgements

This work was supported by project No. 3SGA5789 financed from the SoMoPro II Programme that has acquired a financial grant from the People Programme (Marie Curie Action) of the Seventh Framework Programme of EU according to the REA Grant Agreement No. 291782 and was further co-financed by the South-Moravian Region. This publication reflects only the authors’ views and the Union is not liable for any use that may be made of the information contained therein. This research was also carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II. This study was written at Masaryk university with co-financing of the project “Experimental pharmacological development in neuropsychopharmacology and oncology” number MUNI/A/1284/2015 with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2016 and funds from the Faculty of Medicine MU to junior researcher Jana Ruda-Kucerova.

The authors are grateful for support in behavioural testing and excellent animal care by Jaroslav Nadenicek, and for proof-reading by Heejae Chung and Tony Fong (Toronto, ON).

Statement of interest

None to declare.