Schizophrenia presents as a complex psychiatric disorder characterized by a heterogeneous genetic and neurobiological background. Unfortunately, the prevailing mechanistic remains incompletely elucidated. A dopaminergic basis for schizophrenia has been proposed, implicating an upregulation in dopaminergic neurotransmission. This notion is supported by observations of behavioral hypersensitivity to dopamine receptor-activating drugs in individuals with schizophrenia, as well as postmortem analyses revealing elevated density of dopamine D2 receptors (D2R) in the striatum of schizophrenia patients. Moreover, prior literature has validated the A2A receptor knockout mouse (A2AR-/-) as a preclinical animal model of psychosis.1 Electroconvulsive therapy (ECT) has exhibited significant efficacy as a treatment option for individuals with treatment-resistant schizophrenia (TRS). However, despite its effectiveness, the specific neural mechanisms underlying ECT remain poorly understood. This study aims to investigate whether ECT in A2AR-/- mice can ameliorate psychotic symptoms and to address putative molecular and neurochemical alterations associated with dopamine transmission. As anticipated, A2AR-/- mice exhibited a reduction in basal prepulse inhibition (PPI). Distinctively, immunoblotting analyses revealed elevated density in striatal D2R receptors, while photometry determination described an increased frequency of dopamine peaks per minute, both indicative of dysregulated dopamine dynamics. Remarkably, ECT successfully reversed these abnormalities to a level comparable to that of wild-type mice. Collectively, these findings suggest that ECT not only rescues the psychotic-like phenotype in A2AR-/- mice but is also partially able to restore the altered dopamine dynamics observed in these mice.1. Valle-León, M. et al. Decreased striatal adenosine A2A-dopamine D2 receptor heteromerization in schizophrenia. Neuropsychopharmacology 46, 665–672 (2021).