Participation of glutamatergic and nitrergic systems in the striatal dopamine release induced by isatin, a MAO inhibitor

Abstract

Isatin is a biofactor with different biochemical and pharmacological properties whose effects attract much attention because it is an endogenous inhibitor of the monoamine oxidase in the brain. When exogenously administrated, isatin increases dopamine levels in intact and denervated striatum of rats, an effect that could indicate its potential as a therapeutic agent in Parkinson disease. However, the neurochemical mechanisms by which isatin increases dopamine in the striatum are poorly understood. In the present study, we evaluate the role of the glutamatergic and nitrergic systems in the isatin‐induced dopamine release from rat striatum. Our findings show that the intrastriatal administration of 10 mM isatin significantly increases the in vivo release of dopamine (1,104.7% ± 97.1%), and the amino acids glutamate (428.7% ± 127%) and taurine (221% ± 22%) from rat striatum measured by brain microdialysis. The pretreatment with MK‐801 (500 µM) or AP5 (650 µM) (glutamatergic NMDA receptors antagonists) significantly reduces the effect of isatin on dopamine release by 52% and 70.5%, respectively. The administration of the nitric oxide synthase inhibitors, L‐NAME (100 µM) or 7‐NI (100 µM) also decreases the isatin‐induced dopamine release by 77% and 42%, respectively. These results show that isatin, in addition to increasing dopamine release, also increases glutamate levels, and possibly activates NMDA receptors and nitric oxide production, which can promote a further increase in the dopamine release.

Tobacco and ADHD: A Role of MAO-Inhibition in Nicotine Dependence and Alleviation of ADHD Symptoms

“…The authors suggested in agreement with others, that isatin may increase dopamine levels through greater availability of dopamine in the cytoplasmic reservoir ( Butcher et al, 1988 ; Justo et al, 2016 ). Isatin was further investigated by Faro et al (2021) who found that this MAO-inhibitor likely increases dopamine availability through a) suppression of dopamine metabolism, and b) increasing dopamine release by stimulating exocytotic dopamine production. In summary, there is emerging and convincing evidence of MAO-inhibitors directly and indirectly increasing dopamine in both animal and human models.…”