Fig. 6

Administration of SSRIs elevates Stress Index. (A) SSRIs not only cause an increase in serotonin by blocking serotonin reuptake (the known convention) but also block histamine reuptake leading to a concomitant increase in histamine. This impact is realized in the present model through simultaneous increase in equilibrium histamine and serotonin levels reuptake rates, τ_HA and τ_5HT, respectively, under (A) control, (B) stress, (C) ESCIT administration conditions. The stress intervention condition is associated with a two-fold decrease in tonic histamine supply, I_HA which may be achieved through a histamine reducing drug. The white solid circle refers to S_i for basal parameter values. The graded-color bar denotes the increase in stress index (from blue to red) due to changes in histamine and serotonin concentration. It is observed that blocking histamine leads to a reduced S_i in C. Here, τ_HA = 0.8 s⁻¹, τ_5HT = 0.8 s⁻¹, α = 398 s⁻¹, β = 0.0013 s⁻¹, I_5HT = 118.75 nMs⁻¹. I_HA = 1.25*10⁴ nMs⁻¹ is considered for control condition (A), I_HA = 3.88*10⁴ nMs⁻¹ for the stressed condition (B), and I_HA = 1.94*10⁴ nMs⁻¹ for the stress intervention condition (C)