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Whether these alterations are the consequence of seizure repetition or contribute to the development of epilepsy remains to be clarified. Here, we addressed the involvement of the dopaminergic system in epilepsy onset in\n                      <jats:styled-content style=\"fixed-case\">GAERS<\/jats:styled-content>\n                      s.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Experiments were performed using rats at different stages of brain maturation from three strains according to their increasing propensity to develop absence seizures: nonepileptic control rats (\n                      <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>\n                      s), Wistar Hannover rats, and\n                      <jats:styled-content style=\"fixed-case\">GAERS<\/jats:styled-content>\n                      s. Changes in dopaminergic neurotransmission were investigated using different behavioral and neurochemical approaches: autoradiography of D3R and dopamine transporter, single photon emission computed tomographic imaging, acute and chronic drug effects on seizure recordings (dopaminergic agonists and antagonists), quinpirole\u2010induced yawns and dopamine synaptosomal uptake, microdialysis, brain tissue monoamines, and brain\u2010derived neurotrophic factor quantification.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Autoradiography revealed an increased expression of D3R in 14\u2010day\u2010old\n                      <jats:styled-content style=\"fixed-case\">GAERS<\/jats:styled-content>\n                      s, before absence seizure onset, that persists in adulthood, as compared to age\u2010matched\n                      <jats:styled-content style=\"fixed-case\">NEC<\/jats:styled-content>\n                      s. This was confirmed by increased yawns, a marker of D3R activity, and increased seizures when animals were injected with quinpirole at low doses to activate D3R. We also observed a concomitant increase in the expression and activity of the dopamine transporter in\n                      <jats:styled-content style=\"fixed-case\">GAERS<\/jats:styled-content>\n                      s before seizure onset, consistent with both lowered dopamine basal level and increased phasic responses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      Our data show that the dopaminergic system is persistently altered in\n                      <jats:styled-content style=\"fixed-case\">GAERS<\/jats:styled-content>\n                      s, which may contribute not only to behavioral comorbidities but also as an etiopathogenic factor in the development of epilepsy. The data suggest that an imbalanced dopaminergic tone may contribute to absence epilepsy development and seizure onset, as its reversion by a chronic treatment with a dopamine stabilizer significantly suppressed epileptogenesis. Our data suggest a potential new target for antiepileptic therapies and\/or improvement of quality of life of epileptic patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/epi.16342","type":"journal-article","created":{"date-parts":[[2019,9,19]],"date-time":"2019-09-19T03:13:46Z","timestamp":1568862826000},"page":"2128-2140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Early reduced dopaminergic tone mediated by D3 receptor and dopamine transporter in absence epileptogenesis"],"prefix":"10.1111","volume":"60","author":[{"given":"Fanny","family":"Cavarec","sequence":"first","affiliation":[{"name":"Grenoble Alpes University National Institute of Health and Medical Research U1216, Grenoble Alpes University Hospital Center Grenoble Institute of Neurosciences Grenoble 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