Amygdala-Ventral Pallidum Pathway Decreases Dopamine Activity After Chronic Mild Stress in Rats

Background: Major depressive disorder affects more than 15% of the population across their lifespan. In this study, we used the well-characterized unpredictable chronic mild stress (CMS) model of depression to examine this condition. Methods: Sprague-Dawley rats were presented randomly with mild stressors for 4 weeks, with body weight and sucrose intake monitored weekly. Locomotor activity and elevated plus maze test/forced swim test were conducted on Week 5; ventral tegmental area dopamine (DA) neuron activity was assessed within 1 week after the behavioral test with three indices: DA neuron population activity (defined as the number of spontaneously firing DA neurons); mean firing rate; and percent burst firing (i.e., the proportion of action potentials occurring in bursts). Results: Consistent with previous studies, we found that, compared with control subjects, rats that underwent the CMS procedure were slower in gaining body weight and developed anxiety-and despair-like behavior. We now report a significant decrease in DA neuron population activity of CMS rats, and this decrease is restored by pharmacologically attenuating the activity of either the basolateral nucleus of the amygdala (BLA) or the ventral pallidum (VP). Moreover, pharmacological activation of the amygdala in nonstressed rats decreases DA neuron population activity similar to that with CMS, which is reversed by blocking the BLA-VP pathway. Conclusions: The CMS rat depression model is associated with a BLA-VP-ventral tegmental area inhibition of DA neuron activity. This information can provide insight into the circuitry underlying major depressive disorder and serve as a template for refining therapeutic approaches to this disorder.