Jana Ruda-Kucerova1, Zuzana Babinska1, Petra Amchova1, Tibor Stark1, Filippo Drago2, Alexandra Sulcova3, Vincenzo Micale2,3. 1. a Department of Pharmacology, Faculty of Medicine , Masaryk University , Brno , Czech Republic. 2. b Department of Biomedical and Biotechnological Sciences, Section of Pharmacology , School of Medicine, University of Catania , Catania , Italy. 3. c Behavioral and Social Neuroscience Group , CEITEC - Central European Institute of Technology, Masaryk University , Brno , Czech Republic.
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.
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.
Entities:
Keywords:
Abuse; alcohol; methamphetamine; schizophrenia; sex differences
Authors: Jillian J Weeks; Laura E Rupprecht; Anthony A Grace; Eric C Donny; Alan F Sved Journal: Nicotine Tob Res Date: 2020-02-06 Impact factor: 4.244
Authors: Tibor Stark; Fabio Arturo Iannotti; Serena Di Martino; Martina Di Bartolomeo; Jana Ruda-Kucerova; Fabiana Piscitelli; Carsten T Wotjak; Claudio D'Addario; Filippo Drago; Vincenzo Di Marzo; Vincenzo Micale Journal: Biomolecules Date: 2022-01-10