title: Acute tianeptine treatment selectively modulates neuronal activation in the central nucleus of the amygdala and attenuates fear extinction.
abstract: Antidepressant drugs are commonly prescribed treatments for anxiety disorders, and there is growing interest in understanding how these drugs impact fear extinction because extinction learning is pivotal to successful exposure-based therapy (EBT). A key objective within this domain is understanding how antidepressants alter the activation of specific elements of the limbic-based network that governs such fear processing. Chronic treatment with the antidepressant tianeptine has been shown to reduce the acquisition of extinction learning in rats, yet the drug's acute influence on activation in prefrontal and amygdalar regions, and on extinction learning are not well understood. To assess its influence on cellular activation, rats were injected with tianeptine and Fos immunoreactivity was measured in these regions. Acute tianeptine treatment selectively altered Fos expression within subdivisions of the central nucleus of the amygdala (CEA) in a bidirectional manner that varied in relation to ongoing activation within the capsular subdivision and its prefrontal and intra-amygdalar inputs. This pattern of results suggests that the drug can conditionally modulate the activation of CEA subdivisions, which contain microcircuits strongly implicated in fear processing. The effect of acute tianeptine was also examined with respect to the acquisition, consolidation and expression of fear extinction in rats. Acute tianeptine attenuated extinction learning as well as the recall of extinction memory, which underscores that acute dosing with the drug could alter learning during EBT. Together these findings provide a new perspective for understanding the mechanism supporting tianeptine's clinical efficacy, as well as its potential influence on CEA-based learning mechanisms.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: B P
authors.initials: BP
authors.lastname: Godsil
authors.affiliation: Institut des Maladies Neurodégénératives, Université de Bordeaux, UMR 5293, Bordeaux, France.|ICNRS, Institut des Maladies Neurodégénératives, UMR 5293, Bordeaux, France.
authors.forename: B
authors.initials: B
authors.lastname: Bontempi
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Mailliet
authors.affiliation: Institut de Recherche, Servier (IRS), Suresnes, France.
authors.forename: P
authors.initials: P
authors.lastname: Delagrange
authors.affiliation: Institut de Recherche, Servier (IRS), Suresnes, France.|Spedding Research Solutions, Le Vesinet, France.
authors.forename: M
authors.initials: M
authors.lastname: Spedding
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) UMR_S894, Laboratoire de Physiopathologie des Maladies Psychiatriques, Centre de Psychiatrie et Neurosciences, Paris, France.|Université Paris Descartes, Paris, France.
authors.forename: T M
authors.initials: TM
authors.lastname: Jay
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D066274:Central Amygdaloid Nucleus / Q000166:cytology* / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects*; D005239:Fear / Q000187:drug effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013841:Thiazepines / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D000929:Antidepressive Agents, Tricyclic; D016760:Proto-Oncogene Proteins c-fos; D013841:Thiazepines; C050504:tianeptine