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This effect may be due either to inhibition of carbamyl phosphate synthase (CPS) I by ω-oxidation metabolites (CPS I is the first mitochondrial enzymatic step of the urea cycle) or to decreased synthesis of N -acetyl glutamic acid (NAGA) from acetyl-CoA and glutamate by NAGA synthetase (NAGA is an important cofactor of CPS I)

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Nonetheless, immunohistochemical studies have shown that cocaine decreases glutamate immunoreactivity in presynaptic terminals several brain regions including as the NAcc [79-81], suggesting that some of the observed elevations in extracellular glutamate in response to cocaine are derived from neuronal stores