Maternal lipopolysaccharide treatment differentially affects 5-HT2A and mGlu2/3 receptor function in the adult male and female rat offspring

Positive modulation of α5 GABAA receptors in preadolescence prevents reduced locomotor response to amphetamine in adult female but not male rats prenatally exposed to lipopolysaccharide

“…Hereby, in an elaborate design, involving a repeated administration during the fourth postnatal week of the selected PAM at α5GABA A Rs or the corresponding solvent, we replicated a significant decrease of distance traveled in the habituation and saline trials in the LPS‐females, while the hyporeactivity to amphetamine reached a statistical trend in comparison to SAL females. While concordant to each other, these two sets of our data are apparently at odds with reports from two other studies which were also conducted on Wistar rats and used LPS exposure protocol identical to ours (Wischhof et al, 2015a, 2015b). In one study authors reported an increased baseline locomotion in LPS females at P60, relative to controls (Wischhof et al, 2015a), while in the other study no difference in distance travelled between LPS and control females (P100‐120) was observed (Wischhof et al, 2015b).…”

“…In one study authors reported an increased baseline locomotion in LPS females at P60, relative to controls (Wischhof et al, 2015a), while in the other study no difference in distance travelled between LPS and control females (P100‐120) was observed (Wischhof et al, 2015b). However, it needs to be emphasized that these authors have reported a substantially higher overall activity, at the levels of up to 35 m during the first 5 min, and up to 200 m during 60 min testing (Wischhof et al, 2015a), or around 350 m in just 30 min (Wischhof et al, 2015b); such oversized and inconsistent values impede any comparison with the current results. On the other hand, in a study conducted in 60 day old Sprague Dawley rats born to dams treated with a 50 μg/kg dose of LPS at E15/16, a non‐significant decrease of baseline locomotion in LPS females during 60 min of recording was observed, with absolute levels of activity corresponding well to our data (Harvey and Boksa, 2014a).…”

Sex differences in animal models of schizophrenia shed light on the underlying pathophysiology

“…Therefore, LPS causes differential effects on the developing male and female brain. Indeed, this group further found that males but not females exposed to LPS showed enhanced DOI-induced c-Fos protein expression and an upregulation of prefrontal 5-HT2A receptors (Wischhof et al 2015a). Once again, these studies suggest of a particular vulnerability of the male prefrontal cortex to developmental insult (See figure 1).…”

“…Reduced parvalbumin expression has previously been reported in the prefrontal cortex and hippocampus of schizophrenia patients (Hashimoto et al 2005;Uhlhaas 2013). Furthermore, mGlu2/3 agonist pretreatment attenuated the effects of 5-HT2A agonist DOI on %PPI in saline but not LPS exposed male rats (Wischhof et al 2015a). However, female rats showed a very different response, with saline exposed, but not LPS exposed rats showing reduced PPI following DOI, and no effect of mGlu2/3 agonist pretreatment.…”

Effect of Neuroinflammation on Synaptic Organization and Function in the Developing Brain: Implications for Neurodevelopmental and Neurodegenerative Disorders

“…These changes were associated with long-term increases in hippocampal IL-1β levels, but without changes in microglia or astrocyte density or systemic inflammation, suggesting a local inflammatory effect in the hippocampus (Giovanoli et al, 2016). Other investigations have also shown that maternal viral infection exposure induces schizophrenia-like alterations of 5-HT 2A and mGlu2 receptors in adult offspring (Moreno et al, 2011; Holloway et al, 2013; Wischhof et al, 2015). …”