ETD

• astrocytes
• behavior
• chemogenetic
• cocaine
• Conditioned Place Preference.
• External Globus Pallidus
• reward
• sensitization
• THC

The External Globus pallidus (GPe) is a key nucleus of Basal Ganglia, and it is mostly known for playing a role in locomotion control and refinement. However, it has recently emerged as a central hub in reward-related behavior, particularly in response to cocaine, although underlying mechanisms remain still not clear. GPe has a surprisingly high astrocyte over neurons ratio, suggesting that astrocytes might participate in GPe-mediated behavioral regulation. One of the key regulatory systems controlling astrocytes physiology is the endocannabinoid system: a widespread neuromodulatory system involved in the regulation of several physiological functions. It’s composed mainly of the two endogenous ligands, 2-Arachidonoylglycerol and Anandamide, and the cannabinoid receptors CB1 and CB2. CB1 receptor is largely expressed in the brain, including the GPe. Hypothesizing that Astrocytes and astroglial CB1 could be a functional part of GPe circuitry, we investigated their role in behavioral regulation focusing on locomotion and psychoactive drug-induced reward. Using chemogenetic modulation (DREADD-Gq) of GPe astrocytes during a cocaine-sensitization protocol and cocaine-related place preference (CPP) test, we found that the GPe astrocytes activity may impact on cocaine sensitization and cocaine-related reward. Conversely, CB1 deletion in GPe astrocytes did not affect cocaine reward or THC-induced aversion.