Unaltered cocaine self-administration in the prenatal LPS rat model of schizophrenia

• Prenatal LPS exposure leads to cognitive dysfunction.
• Working memory deficits are worse in females.
• LPS-animals showed impaired PPI.
• No alterations in cocaine self-administration

Although cocaine abuse is up to three times more frequent among schizophrenic patients, it remains unclear why this should be the case and whether sex influences this relationship. Using a maternal immune activation model of schizophrenia, we tested whether animals at higher risk of developing a schizophrenia-like state are more prone to acquire cocaine self-administration behavior, and whether they show enhanced sensitivity to the reinforcing actions of cocaine or if they are resistant to extinction. Pregnant rats were injected with lipopolysaccharide on gestational day 15 and 16, and the offspring (both male and female) were tested in working memory (T-maze), social interaction and sensorimotor gating (prepulse inhibition of the acoustic startle response) paradigms. After performing these tests, the rats were subjected to cocaine self-administration regimes (0.5 mg/kg), assessing their dose–response and extinction. Male rats born to dams administered lipopolysaccharide showed impaired working memory but no alterations to their social interactions, and both male and female rats showed prepulse inhibition deficits. Moreover, similar patterns of cocaine self-administration acquisition, responsiveness to dose shifts and extinction curves were observed in both control and experimental rats. These results suggest that the higher prevalence of cocaine abuse among schizophrenic individuals is not due to a biological vulnerability directly associated to the disease and that other factors (social, educational, economic, familial, etc.) should be considered given the multifactorial nature of this illness.