Two repeated maternal separation procedures differentially affect brain 5-hydroxytryptamine transporter and receptors in young and adult male and female rats

Abstract

Early environment is a known determinant for individual differences in vulnerability for adult psychopathology, e.g., ethanol addiction. One underlying mechanism could be dysfunction in serotonergic neurotransmission. This study focused on the methodological considerations regarding an animal model for studying effects of early environment, maternal separation (MS), using two different paradigms. Age- and sex-specific effects on brain stem 5-hydroxytryptamine (5-HT) transporter and receptors were examined. Male and female rat pups were assigned to either litter-wise MS for 15 or 360 min (MS15 l or MS360 l) or individual MS for 15 or 360 min (MS15 i or MS360 i) daily during postnatal days 1–21. Normal animal facility reared rats were used as controls. Analyses were performed in young and adult rats. As compared to the other males, MS15 l males had lower 5-HT 1A and 5-HT 2C receptor mRNA expression at both ages, lower 5-HT 2A receptor mRNA when young and lower 5-HTT mRNA expression when adult. In contrast, adult MS15 l females had higher 5-HT 2C receptor mRNA expression than other female rats. The strong impact of MS15 l on 5-HT-related genes was either transient or persistent depending on sex and fewer effects on gene expression were observed in females than in males. This study shows the importance of tactile contact for the consequences of short but not prolonged MS, as evidenced by major differences between MS15 l and MS15 i. The results suggest that MS15 i is less suitable than MS15 l to simulate a protective environment in studies of, for instance, ethanol addiction processes.