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Schizophrenia is a chronic disease affecting 1% worldwide population, of which 30% are refractory to the available treatments: thus, searching for new pharmacological targets is imperative. The acute and repeated ketamine administration are validated preclinical models that recreate the behavioral and neurochemical features of this pathology, including the parvalbumin-expressing interneurons dysfunction. Angiotensin II, through AT 1 receptors (AT 1 -R), modulates the dopaminergic and GABAergic neurotransmission. We evaluated the AT 1 -R role in the long-term neuronal activation and behavioral alterations induced by repeated ketamine administration. Adult male Wistar rats received AT 1 -R antagonist candesartan/vehicle (days 1–10) and ketamine/saline (days 6–10). After 14 days of drug-free, neuronal activation and behavioral analysis were performed. Locomotor activity, social interaction and novel object recognition tests were assessed at basal conditions or after ketamine challenge. Immunostaining for c-Fos, GAD67 and parvalbumin were assessed after ketamine challenge in cingulate, insular, piriform, perirhinal, and entorhinal cortices, striatum, and hippocampus. Additionally, to evaluate the AT 1 -R involvement in acute ketamine psychotomimetic effects, the same behavioral tests were performed after 6 days of daily-candesartan and a single-ketamine administration. We found that ketamine-induced long-lasting schizophrenia-like behavioral alterations, and regional-dependent neuronal activation changes, involving the GABAergic neurotransmission system and the parvalbumin-expressing interneurons, were AT 1 -R-dependent. The AT 1 -R were not involved in the acute ketamine psychotomimetic effects. These results add new evidence to the wide spectrum of action of ketamine and strengthen the AT 1 -R involvement in endurable alterations induced by psychostimulants administration, previously proposed by our group, as well as their preponderant role in the development of psychiatric pathologies. • Ketamine induced acute and long-term schizophrenia-like behavioural alterations. • AT1-R play a key role in behavioural alterations induced by repeated Ketamine. • Ketamine induced endurable GABAergic parvalbumin-expressing neurons dysfunction. • AT1-R has a critical role in long-term GABAergic neuroadaptive changes. • AT1-R is not involved in acute Ketamine psychotomimetic effects. [ABSTRACT FROM AUTHOR]