Stress Controllability Modulates Basal Activity of Dopamine Neurons in the Substantia Nigra Compacta

Prolonged stress induces neural maladaptations in the mesolimbic dopamine (DA) system and produces emotional and behavioral disorders. However, the effects of stress on activity of DA neurons are diverse and complex that hinge on the type, duration, intensity, and controllability of stressors. Here, controlling the duration, intensity, and type of the stressors to be identical, we observed the effects of stressor controllability on the activity of substantia nigra pars compacta (SNc) DA neurons in mice. We found that both lack and loss of control (LOC) over shock enhance the basal activity and intrinsic excitability of SNc DA neurons via modulation of I(h) current, but not via corticosterone serum level. Moreover, LOC over shock produces more significant enhancement in the basal activity of SNc DA neurons than that produced by shock per se, and therefore attenuates the response to natural reward. This attenuation can be reversed by control over shock. These results indicate that although chronic stress per se tends to enhance the basal activity of SNc DA neurons, LOC over the stressor is able to induce a larger enhancement in the basal activity of SNc DA neurons and produce more severe behavioral deficits. However, control over stress ameliorates the deleterious effects of stress, highlighting the role of stress controllability.