Sex-Specific Transcriptional Changes in Response to Adolescent Social Stress in the Brain’s Reward Circuitry

Long-Term Impacts of Post-weaning Social Isolation on Nucleus Accumbens Function

“…Similar effects were observed after aSI on baseline mRNA expression in male and female mice. With the exception of Unc13c mRNA expression in the VTA where aSI males had less Unc13c , aSI had no effect on baseline gene expression of these molecules in the NAc or VTA ( 121 ). However, cocaine evoked changes in mRNA expression were observed across both brain regions and sexes.…”

“…In rats, SI-R increases TH protein-expression in synaptoneurosomes from the NAc when compared to GH males ( 120 ), which could explain the increased evoked dopamine observed after SI-R discussed above (section Adolescent Social Isolation and Disruption of Cellular Function With in the NAc). However, these effects may be species, molecule, and/or isolation type specific as a recent study investigating gene expression changes in mice ( 121 ), found that Th mRNA expression was unaffected by aSI in males and females in both the NAc and VTA. Additionally, important sex-specific changes in Th mRNA expression in the VTA, the presumed location of Th mRNA transcription, were observed after exposure to cocaine ( Figure 3B ).…”

“…When animals were exposed to repeated cocaine injections (10 days, 7.5 mg/kg), aSI males and females display opposite regulation of Th expression: females upregulate and males downregulate Th expression when compared to their same-sex GH counterparts. Additionally, aSI males but not females downregulated Th gene expression after only one injection of cocaine ( 121 ). Together, these data suggest that adolescent social isolation alters the synthesis of dopamine in a sex, species and stimulus-specific manner.…”

“…Vesicular monoamine transporter (VMAT) is the protein necessary for packaging dopamine into vesicles ( Figure 3A ). Studies investigating VMAT protein levels ( 120 ) and RNA levels ( 121 ) found that adolescent social isolation has no effect on expression in the NAc of adult male rats ( 120 ) or male and female mice ( 121 ). However, aSI induced sex-specific changes in gene expression of VMAT (gene name: Slc18a2 ) in the VTA ( Figure 3B ), the presumed source of VMAT protein in terminals of dopaminergic neurons ( Figure 3A ).…”

“…However, aSI induced sex-specific changes in gene expression of VMAT (gene name: Slc18a2 ) in the VTA ( Figure 3B ), the presumed source of VMAT protein in terminals of dopaminergic neurons ( Figure 3A ). While Slc18a2 expression was unaffected at baseline, when animals were exposed to repeated cocaine injections (7.5 mg/kg for 10 days), sex-specific regulation of expression was again observed: females upregulated whereas males downregulated Slc18a2 expression [ Figure 3B ; ( 121 )]. These data suggest that baseline packaging of dopamine into vesicles is unaffected by adolescent social isolation.…”