Jana Rudá

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.

Differential characteristics of ketamine self-administration in the olfactory bulbectomy model of depression in male rats

Ketamine has been extensively studied for its antidepressant potential, with promising results in both preclinical and clinical studies. However, concerns regarding its abuse liabilities greatly limit its potential to become an approved treatment for depression. Therefore, a better understanding the risks and benefits of ketamine use in depression is needed. This study aimed to assess the characteristics of operant intravenous (IV) ketamine self-administration and relapse-like behavior in the olfactory bulbectomy (OBX) model of depression in male rats. Twenty-five male Wistar rats were divided randomly into 2 groups; in 1 group the bilateral olfactory bulbectomy was performed, whereas the other group was sham-operated. Intravenous self-administration of ketamine (.5 mg/kg/infusion) was conducted under a fixed ratio 1 schedule of reinforcement. After reaching stable drug intakes, rats then underwent a 14-day period of forced abstinence followed by a drug-free relapse-like session. The forced swim test was conducted before the commencement of the self-administration protocol and on the 1st day of abstinence. Consistent with findings in previous studies on other substances, OBX animals showed increased operant IV ketamine self-administration. In contrast, ketamine-seeking behavior in the OBX group did not differ from sham-operated animals during the relapse-like session, whereas previous studies on other psychostimulants like methamphetamine and cocaine reported increases. Our findings suggest substantially different underlying neuroadaptations between chronic ketamine and psychostimulant exposure.