Investigating Tryptophan Hydroxylase Immunoreactivity in the Dorsal Raphe of Rats Exposed to Early Adversity

Prior studies link anxiety to alterations in serotonergic neurotransmission. Tao and Menard (unpublished data) found that female rats exposed to intermittent physical stress during early adolescence display greater levels of anxiety-like behaviours when tested as adults in social interaction tests. Interestingly, these behavioural changes were associated with changes in serotonin (5-HT) fiber density in the medial prefrontal cortex. Whether these changes in 5-HT fibre density are accompanied by changes in the number of 5-HT-producing cells in the dorsal raphe is not known. To examine this research question, tryptophan-hydroxylase (TPH) immunoreactivity (-IR) was used to label 5-HT cells in the dorsal raphe. Half the animals from the original adolescent stress study were exposed to IPS, and the remaining animals were handled only, serving as the control (CON) group. In adulthood, half of each of those groups were tested in the SI test. The remaining animals were not behaviourally tested, serving as home-cage controls (HCC). A two-factor analysis of variance will be performed with Treatment (IPS vs CON) and Testing (SI vs HCC) as the two factors. It is expected that, regardless of Testing, IPS rats will display higher levels of TPH-IR in the dorsal raphe than no-stress controls. The number of TPH-IR-positive cells will also be correlated with archival behavioural data. It is expected that that higher levels of TPH-IR will be associated with higher levels of anxiety-like behaviour. This study provides insights into the role that early adversity plays in shaping the structure and function of the brain’s serotonergenic system.