Postnatal maturation of cortical serotonin lateral asymmetry in gerbils is vulnerable to both environmental and pharmacological epigenetic challenges

Abstract

Long-term effects of postnatal differential rearing conditions and/or early methamphetamine (MA) application on serotonin (5-HT) fibre density were investigated in several cortical areas of both hemispheres of gerbils. The aim of this study was twofold: (1) Is the 5-HT fibre innervation of the cerebral cortex lateralised, and (2) if so, do postnatal environmental conditions and/or an early drug challenge interfere with development of 5-HT cerebral asymmetries? For that purpose, male gerbils were reared either under semi-natural or restricted environmental and social conditions, under both conditions once (on postnatal day 14) being treated with either a single dose of MA (50 mg/kg, i.p.) or saline. On postnatal day 110, 5-HT fibres were immunohistochemically stained and innervation densities quantified in prefrontal cortex, insular cortex, frontal cortex, parietal cortex, and entorhinal cortex. It was found that (1) 5-HT innervation in the cerebral cortex was clearly lateralised; (2) direction and extent of this asymmetry were not uniformly distributed over the different areas investigated; (3) both early methamphetamine challenge and rearing condition differentially interfered with adult 5-HT cerebral asymmetry; (4) combining MA challenge with subsequent restricted rearing tended to reverse the effects of MA on 5-HT cerebral asymmetry in some of the cortical areas investigated; and (5) significant responses in 5-HT cerebral asymmetry only occurred in prefrontal and entorhinal association cortices. The present findings suggest that the ontogenesis of cortical laterality is influenced by epigenetic factors and that disturbances of the postnatal maturation of lateralised functions may be associated with certain psychopathological behaviours.