Adolescent social isolation induces sex- and region-dependent changes in corticolimbic neurotransmitter profiles

Adolescence is a critical period of corticolimbic maturation during which social experiences shape neurochemical systems involved in emotional regulation. Social isolation during this stage may therefore produce sex- and region-dependent alterations in neurotransmitter profiles. We examined the effects of isolated rearing (IR) on monoamines and their metabolites, glutamate (Glu), and GABA in male and female Wistar rats (n=35). Animals were socially reared (SR) or isolated from postnatal day 21 (PND21) and gonadectomised at PND45, after pubertal hormone exposure. At PND55, the medial prefrontal cortex (mPFC), lateral septum (LS), nucleus accumbens (NAc), dorsal hippocampus (dHIP), and amygdala were micropunched and analysed by HPLC. IR reduced DOPAC/DA and Glu in the mPFC but increased DOPAC/DA in the dHIP. In the LS, IR reduced DA and altered DOPAC/DA in a sex-dependent manner, with higher turnover in isolated males. The amygdala was the most broadly affected region: IR reduced DOPAC, 5-HIAA, and GABA levels, while dopaminergic and serotonergic alterations were sex-dependent. Neurochemical measures that were higher in SR females were attenuated under IR. In contrast, the NAc showed only a sex effect on DOPAC/DA. These findings demonstrate that adolescent social isolation does not produce a uniform neurochemical response but induces region- and sex-dependent alterations across corticolimbic systems, with particularly pronounced effects in the amygdala.