Activation of the basolateral or the central amygdala dampened the incentive motivation for food reward on high fixed-ratio schedules.

The amygdala plays crucial roles in emotional processing, motivated behaviors, and stress responses. It receives sensory information and modulates fear- and anxiety-related behaviors. Neuronal activations are induced in the basolateral complex of the amygdala (BLA) and the central nucleus of the amygdala (CeA) when exposing to acute stress, leading to increased alertness and proper behavioral adaptation. Previous studies have shown that animals displayed a decrease in appetitive motivated behaviors under stress conditions. However, whether the hyperactive amygdala is responsible for the decrease in appetitive motivated behaviors remains unknown. In this study, we aimed to examine the role of BLA or CeA activation in effort-based motivated behavior. We pharmacologically activated the BLA or the CeA with N-methyl-D-aspartate (NMDA) before the lever-pressing for food reward test on different fixed-ratio (FR) schedules (FR1, FR16, or FR32) in male Long-Evans rats. Our data showed that activation of either the BLA or the CeA with NMDA (0.05 µg in 0.5 µl per site) decreased the lever-pressing behavior on higher FR schedules of FR16 and FR32, but not on the FR1 test. Importantly, locomotor activity and free-feeding food intake were intact under amygdala activation, suggesting that the decrease in lever-pressing behavior was not due to motor disablement or decreased appetite. These results suggested that activation of the BLA or the CeA negatively impaired the effort-based motivated behavior that the animals were less willing to work for food reward.

Analysis of lateral orbitofrontal cortex activation on acquisition of fear extinction and neuronal activities in fear circuit.

Inappropriate fear expression and failure of fear extinction are commonly seen in patients with post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). Among the patients, aberrant and asymmetric activation of the lateral orbitofrontal cortex (lOFC) is reported in some clinical cases. In this study, we aimed to examine the role of lOFC activation in extinction acquisition and explore the potential functional lateralization of lOFC on extinction. We bilaterally or unilaterally activated the lOFC with N-methyl-D-aspartate (NMDA) before fear extinction acquisition in rats. Our data suggested that both left and bilateral lOFC activation interfered with the in-session expression of conditioned fear, whereas activation of the right lOFC did not. In addition, pre-extinction unilateral or bilateral activation of the lOFC, regardless of the side, impaired the acquisition of fear extinction. We also quantified the neuronal activities during the late phase of extinction with immunohistochemical approach. Our data showed that activation of the lOFC increased the neuronal activities on the injection side(s) in the medial prefrontal cortex (mPFC), the lateral amygdala (LA), the basolateral amygdala (BLA; preferentially the non-GABAergic neurons), and the medial intercalated cells (mITC; preferentially the right side). To conclude, aberrant activation of the lOFC during extinction disturbed the excitatory/inhibitory balance of neuronal activities in fear-related brain regions, which interfered with the expression of conditioned fear and impaired the acquisition of fear extinction.