Sexually dimorphic recruitment of dopamine neurons into the stress response circuitry.

Several previous studies in mammalian systems have shown sexually dimorphic behaviors, neuroendocrine changes, and alterations in neurotransmitter release in response to stress. Additionally, men and women are differentially vulnerable to stress-related pathologies, which have led to the hypothesis that the stress response circuitry differs depending on sex. We used the genetic tractability of Drosophila to manipulate pre- or post-synaptic dopamine signaling in transgenic animals, which were assayed for several parameters of locomotion and heart rate following exposure to two environmental stressors, starvation and oxidative stress. Our results show significant differences in the stress response for males and females by analyzing heart rate, centering time, and high mobility in addition to other locomotor parameters with translational relevance. These data demonstrate that both pre- and post-synaptic neurons are differentially recruited into the dopaminergic stress response circuitry for males and females. Our results also show that the response circuits differ depending on the stressor and behavioral output. Furthermore, our studies provide a translatable Drosophila model for further elucidation of factors involved in the sexually dimorphic recruitment of neurons into the stress response circuitry.