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Although much less characterized, epileptiform activities, usually triggered by disruption of the glutamate and GABA balance, have also been reported to involve the dopaminergic transmission. Using a combination of biochemical, immunohistochemical, electrophysiological, and behavioral approaches we have investigated the consequences of repeated stimulation of D1R using the selective D1R\u2010like agonist SKF81297. Here, we report that repeated systemic administration of SKF81297 induces kindled seizures in mice. These seizure episodes parallel the hyperactivation of the mTOR signaling in the hippocampus, leading to disrupted long\u2010term potentiation (LTP) in the dentate gyrus (DG) and altered recognition memories. The mTOR inhibitor rapamycin delays the development of SKF81297\u2010induced kindled seizures, and rescues LTP in the DG and object recognition. Our results show that repeated stimulation of D1R is sufficient to induce generalized seizures leading to the overactivation of mTOR signaling, disrupted hippocampal plasticity, and impaired long\u2010term recognition memories. This work highlights the interest of mTOR inhibitors as therapeutic strategies to reverse plasticity and cognitive deficits. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/hipo.22327","type":"journal-article","created":{"date-parts":[[2014,7,5]],"date-time":"2014-07-05T09:37:21Z","timestamp":1404553041000},"page":"1466-1481","source":"Crossref","is-referenced-by-count":35,"title":["Repeated stimulation of dopamine D1\u2010like receptor and hyperactivation of mTOR signaling lead to generalized seizures, altered dentate gyrus plasticity, and memory deficits"],"prefix":"10.1002","volume":"24","author":[{"given":"Giuseppe","family":"Gangarossa","sequence":"first","affiliation":[{"name":"CNRS, UMR\u20105203, Institut de G\u00e9nomique Fonctionnelle  Montpellier France"},{"name":"INSERM, U661  Montpellier France"},{"name":"Universit\u00e9s de Montpellier 1 &amp; 2 UMR\u20105203 Montpellier 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