Maternal immune activation and estrogen receptor modulation induce sex-specific dopamine-related behavioural and molecular alterations in adult rat offspring

• DOI: 10.1016/j.bbi.2024.02.034
• Publication Date: 2024-02-29T09:36:02Z
• Authors: Sophie R. Debs; Illya Conn; Brendan Navaneethan; Andriane G. Penklis; Urs Meyer; Simon Killcross; Cynthia Shannon W...; Tertia D. Purves-...
• Keywords: Raloxifene

Dopamine dysregulation contributes to psychosis and cognitive deficits in schizophrenia that can be modelled rodents by inducing maternal immune activation (MIA). The selective estrogen receptor (ER) modulator, raloxifene, improve cognition men women with schizophrenia. However, few studies have examined how raloxifene may exert its therapeutic effects mammalian brain both sexes during young adulthood (age relevant most prevalent age at diagnosis). Here, we tested the extent which alters dopamine-related behaviours transcripts adult rats, control MIA-exposed females males. We found increased amphetamine (AMPH)-induced locomotor activity female controls, contrast, reduced AMPH-induced male MIA offspring. did not detect overt prepulse inhibition (PPI) or offspring, yet enhanced PPI Whereas, ameliorated startle responsivity In substantia nigra (SN), Drd2s mRNA raloxifene-treated offspring without MIA, Comt placebo-treated relative controls. These data demonstrate an underlying dopamine animals become more apparent treatment, involve alterations levels breakdown processes SN. Our findings support sex-specific, differential behavioural responses ER modulation compared beneficial of treatment on only.