title: Lurasidone exerts antidepressant properties in the chronic mild stress model through the regulation of synaptic and neuroplastic mechanisms in the rat prefrontal cortex.
abstract: BACKGROUND
  Major depression is associated with several alterations, including reduced neuronal plasticity and impaired synaptic function, which represent an important target of pharmacological intervention.
  
  
  METHODS
  In the present study, we have investigated the ability of the antipsychotic drug lurasidone to modulate behavioral and neuroplastic alterations in the chronic mild stress model of depression.
  
  
  RESULTS
  Rats that show reduced sucrose consumption after 2 weeks of chronic mild stress have reduced expression of the pool of Bdnf transcripts with the long 3' untranslated region (3'-UTR) that may be targeted to the synaptic compartment, suggesting the contribution of the neurotrophin to the behavioral dysfunction produced by chronic mild stress. The downregulation of Bdnf expression persisted also after 7 weeks of chronic mild stress, whereas chronic lurasidone treatment improved anhedonia in chronic mild stress rats and restored Bdnf mRNA levels in the prefrontal cortex. Moreover, chronic lurasidone treatment was able to normalize chronic mild stress-induced defects of Psd95 and Gfap as well as changes in molecular regulators of protein translation at the synapse, including mTOR and eEF2.
  
  
  CONCLUSIONS
  These results demonstrate that lurasidone shows antidepressant properties in the chronic mild stress model through the modulation of synaptic and neuroplastic proteins. Such changes may contribute to the amelioration of functional capacities, which are deteriorated in patients with major depression and stress-related disorders.
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy (Drs Luoni, Macchi, Molteni, and Riva); Institute of Pharmacology, Polish Academy of Sciences, Kracow, Poland (Dr Papp).
authors.forename: Alessia
authors.initials: A
authors.lastname: Luoni
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy (Drs Luoni, Macchi, Molteni, and Riva); Institute of Pharmacology, Polish Academy of Sciences, Kracow, Poland (Dr Papp).
authors.forename: Flavia
authors.initials: F
authors.lastname: Macchi
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy (Drs Luoni, Macchi, Molteni, and Riva); Institute of Pharmacology, Polish Academy of Sciences, Kracow, Poland (Dr Papp).
authors.forename: Mariusz
authors.initials: M
authors.lastname: Papp
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy (Drs Luoni, Macchi, Molteni, and Riva); Institute of Pharmacology, Polish Academy of Sciences, Kracow, Poland (Dr Papp).
authors.forename: Raffaella
authors.initials: R
authors.lastname: Molteni
authors.affiliation: Dipartimento di Scienze Farmacologiche e Biomolecolari, Università degli Studi di Milano, Milan, Italy (Drs Luoni, Macchi, Molteni, and Riva); Institute of Pharmacology, Polish Academy of Sciences, Kracow, Poland (Dr Papp). m.riva@unimi.it.
authors.forename: Marco A
authors.initials: MA
authors.lastname: Riva
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002908:Chronic Disease; D003866:Depressive Disorder / Q000188:drug therapy* / Q000378:metabolism; D004195:Disease Models, Animal; D000076122:Disks Large Homolog 4 Protein; D054736:Elongation Factor 2 Kinase / Q000378:metabolism; D027342:Excitatory Amino Acid Transporter 2 / Q000378:metabolism; D050580:Excitatory Amino Acid Transporter 3 / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D000069056:Lurasidone Hydrochloride / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D017208:Rats, Wistar; D013315:Stress, Psychological; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D027342:Excitatory Amino Acid Transporter 2; D050580:Excitatory Amino Acid Transporter 3; D005904:Glial Fibrillary Acidic Protein; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D012333:RNA, Messenger; C493466:Slc17a7 protein, rat; C493398:Slc1a1 protein, rat; C493395:Slc1a2 protein, rat; D050598:Vesicular Glutamate Transport Protein 1; C546845:mTOR protein, rat; C517691:Eef2k protein, rat; D058570:TOR Serine-Threonine Kinases; D054736:Elongation Factor 2 Kinase; D000069056:Lurasidone Hydrochloride
keywords: BDNF; chronic mild stress; glutamate; lurasidone; synaptic mechanisms