The Slippery Slope: Exploring the Role of the Central Amygdala in Creating Compulsive Preference

Substance use disorders involve compulsive preference for drugs of abuse over better and healthier options. It has been shown that optogenetic stimulation of the Central Amygdala (CeA) creates an addiction-like preference for a stimulation-paired reward. The preference persists even when choosing this reward is maladaptive. Little is known about how this compulsive preference persists. The present study evaluates the relative role of three theories of addiction in generating CeA-induced compulsive preference: habit formation, accelerated learning, and decision making influenced by an increased value of drug associated stimuli. Using optogenetics, the CeA was stimulated during various tasks to see how behavior was changed as compared to viral controls. The first experiment examined if the CeA is reinforcing habitual behavior by causing subjects to perseverate on one stimulation paired choice as opposed to maintaining flexible behavior in a learning task. Secondly, it was asked if stimulation of the CeA on correct answers of this task could accelerate learning by committing reinforced answers to memory faster than incorrect, non-reinforced answers. The last part of the study examined if the CeA adds motivational value to stimuli associated with rewards, and not rewards exclusively. This study shows evidence for a role of the CeA in adding motivational value to rewards, but not stimuli associated with these rewards. This motivational value for CeA stimulation paired rewards was shown to be compulsive, as it persisted in the face of more plentiful rewards. However, this compulsive preference could only exist when subjects had already developed a preference for a CeA stimulation paired reward before it was devalued. These results suggest that the CeA can create a powerful preference for rewards that continues even when these rewards become devalued, modeling the transition from casual drug use to addiction.