The Extended Amygdala in Appetitive Motivation for Reward: Role of the Bed Nucleus of the Stria Terminalis.

Abstract

The extended amygdala is an emerging neuroanatomical concept for a basal forebrain macrosystem, containing the bed nucleus of the stria terminalis (BNST) and several other highly interconnected nuclei. BNST has received increasing attention following the discovery that it connects to limbic brain regions involved in stress, homeostasis, and reward. Most of the literature on BNST function emphasizes its role in aversive motivational processes such as stress, anxiety and drug withdrawal. However, some circumstantial evidence suggests that BNST also plays a role in appetitive motivation (e.g., reward ‘wanting’), although direct tests have not yet been made. Here, I present a series of experiments designed to provide the first direct evidence for a role of BNST in appetitive motivation for food reward. I found that stimulation of µ-opioid receptors in BNST potently increased eating behavior in non-deprived rats. By contrast, temporary suppression of BNST yielded increased aversive behaviors such as defensive treading and escape dashes. Was eating caused by BNST stimulation truly appetitive or only instead due to aversive stress? I found that rats exhibited a conditioned place preference for an environment paired with µ-opioid stimulation in BNST, confirming that this stimulation produced primarily appetitive effects. I also found that opioid stimulation in BNST diffusely increased the motivational magnet qualities of a conditioned stimulus for a food reward in an autoshaping test. This stimulation spilled elevated motivation into inappropriate moments, enhancing responding even when the reward cue was absent. By contrast, stimulation of another limbic structure, nucleus accumbens, only increased motivational attractiveness in the presence of the cue. Accordingly, stimulation of nucleus accumbens, but not BNST, also elevated an animal’s willingness to earn presentations of the autoshaping conditioned stimulus in conditioned instrumental reinforcement testing. Finally, I showed that increased feeding after µ-opioid stimulation in BNST occurs in spite of decreased hedonic ‘liking’ for sweet taste. Together, these experiments provide direct evidence that BNST mediates appetitive motivation, and further clarify the function of µ-opioid circuits in the extended amygdala.