ELECTROCONVULSIVE STIMULATION REDUCES PSYCHOTIC-LIKE BEHAVIORS AND RESCUES DOPAMINE DYNAMICS IN ADENOSINE A<SUB >2A</SUB> RECEPTOR-DEFICIENT MICE

Schizophrenia is a complex psychiatric disorder characterized by a heterogeneous genetic and neurobiological background, in which the underlying pathophysiological mechanisms are not fully understood. A prominent hypothesis proposes a dysregulation of dopaminergic neurotransmission, supported by behavioral hypersensitivity to dopamine receptor agonists and an increase in the density of the striatal dopamine D₂ receptor observed in patients. The mouse lacking adenosine A_2A receptor (A_2AR^‑/‑) has been established as a relevant preclinical model of psychosis. Electroconvulsive therapy (ECT) is an effective intervention for treatment-resistant schizophrenia; however, its neurobiological mechanisms of action remain largely unclear. In this study, we investigated whether electroconvulsive stimulation could ameliorate psychotic‑like behaviors and normalize dopamine signaling alterations in A_2AR^‑/‑ mice. Behavioral analyses revealed a significant reduction in basal prepulse inhibition in A_2AR^‑/‑ mice compared with wild‑type controls. In parallel, fiber photometry recordings demonstrated an increased frequency of spontaneous dopamine transients, indicative of dysregulated dopamine dynamics. In particular, electroconvulsive stimulation restored prepulse inhibition performance and normalized dopamine transient frequency to levels comparable to those of wild-type mice. These results demonstrate that electroconvulsive stimulation reverses both behavioral and neurochemical abnormalities associated with adenosine A_2AR deficiency. Overall, our findings suggest that the therapeutic efficacy of electroconvulsive stimulation in psychosis-related disorders may be mediated, at least in part, by normalization of aberrant dopamine dynamics.