Optogenetic Insights into Central Amygdala Motivational Mechanisms

Abstract

A characteristic hallmark of addiction is the focused pursuit of drugs at the expense of other life rewards. Focusing motivation towards the appropriate target and at appropriate times is an adaptive strategy, and helpful in directing motivation towards targets such as food or sex through forming of associations with neutral environmental stimuli. However, this strategy can be hijacked by drugs of abuse to cause pathological pursuit of drugs and their related cues rather than normal life rewards in an intense fashion. Amygdala circuitry may be a crucial mechanism by which focused motivation for normal life rewards can become hijacked by drugs of abuse to create excessive motivation focused on pursuing drugs of abuse. The experiments described here used optogenetic techniques to dissect the psychological and neurobiological mechanisms by which amygdala circuitry generates incentive motivation focused onto particular targets. We first paired optogenetic CeA excitation with earning a particular sugar reward, when rats were choosing between that and an identical sugar reward lacking CeA excitation. CeA excitation made its paired reward the sole target of pursuit - both narrowing and enhancing motivation for that reward, even though both rewards available were identical. Similarly, CeA excitation paired with a cocaine reward made that particular cocaine infusion the sole target of motivation compared to an identical cocaine infusion available, which lacked CeA excitation. In both cases, CeA excitation was not reinforcing alone, indicating that CeA excitation was directly transforming the brain’s representation of its associated reward (sucrose or cocaine) to make it more ‘wanted’. Using taste reactivity techniques, we show that CeA excitation does not alter hedonic ‘liking’ of sucrose, and thus is not the reason rats ‘want’ rewards paired with CeA excitation (they do not ‘like’ it more). Further, we demonstrate that we can gain control of which reward gets ‘wanted’ most by pairing CeA excitation arbitrarily with either sucrose or cocaine, when rats are choosing between the two different rewards. Finally, pasting CeA excitation onto a known aversive target enhances attraction and investigation of that stimulus while also reducing defensive behaviors. In all situations, CeA excitation being temporally pasted onto a motivationally relevant stimulus, makes that stimulus the sole object of desire. Evidence within each experiment supports the notion that CeA excitation is likely doing so by enhancing the attribution of incentive salience to those stimuli and their related cues. These findings demonstrate that a hijacked CeA circuitry is sufficient to control reward ‘wanting’, even to irrational and dangerous levels, highlighting a potentially crucial role for amygdala-related circuitry in focused and irrational pursuit occurring in addiction.