The central amygdala (CeA) is known as an important area that regulates both behavioral and physiological stimuli. The CeA is composed of the centrolateral amygdala and the centromedial amygdala, both of which have many GABA neurons in them. It also functions in many reward pathways, including a GABA pathway involving cocaine-seeking behavior that projects neurons to the nucleus accumbens (NAc). In this set of experiments, a chemogenetic method was used to study the effects of inhibiting the GABAergic projections from the CeA to the NAc. Additionally, it has been found that the majority of GABA neurons in the CeA to NAc pathway contain GLP-1Rs. GLP-1 is a gut neuropeptide that modulates neural circuits in response to drug intake. It has been hypothesized that GLP-1Rs cause an attenuation of drug reinstatement, including that of cocaine. 

It was found that reducing the effect of GABA projections from the CeA to the NAc reduces the attenuation of cocaine-seeking behavior during reinstatement. Future plans include using Exendin-9, a GLP-1R antagonist, to determine whether GLP-1R-expressing cells are the specific cells that cause the attenuation of cocaine-seeking behavior, which they likely are due to the previously stated fact that a majority of GABA neurons in the CeA to NAc pathway are GLP-1R-expressing. Another future idea is to study other targets along this possible GLP-1R-expressing pathway, like the NTS, which serves as an input to the CeA, or the VTA, which typically deals with dopamine pathways. The pathway can also be studied backwards from the NAc to the CeA to identify a possible negative feedback mechanism that occurs in response to not only cocaine-seeking behavior, but drug-seeking behavior in general. Ultimately, our goal is to identify a novel GLP-1R-expressing circuit that could be targeted to reduce cocaine relapse and cocaine abstinence-induced anxiety, which is modeled by our reinstatement period of our paradigm.