Nitrous Oxide and Cortico-Limbic Function in Aggression

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Project Summary In this application, we propose to build on previous work regarding the role of glutamate in impulsive aggression. Both preclinical animal studies and recent human studies from our labs and other labs support the hypothesis that glutamate is an important modulator that facilitates aggressive behavior. In this study, we propose to use an FDA approved glutamatergic modulator, Nitrous Oxide (N2O), to determine if N2O has the ability to normalize cortico-limbic circuits previously associated with impulsive aggressive behavior in humans. Impulsive aggressive, and healthy non-aggressive control, study participants will undergo two inhalation protocols (50% N2O / 50% O2 as active and 50% N2 / 50% O2 as control) separated by at least one week and undergo an fMRI Scan 24 hours after each inhalation study session. If this mechanistic study demonstrates that N2O inhalation can normalize the functioning of these circuits, N2O may represent a candidate as an anti-aggressive agent.