title: Gene expression related to serotonergic and glutamatergic neurotransmission is altered in the flinders sensitive line rat model of depression: Effect of ketamine.
abstract: Major depressive disorder (MDD) is associated with dysfunctional serotonergic and glutamatergic neurotransmission, and the genetic animal model of depression Flinders Sensitive Line (FSL) rats display alterations in these systems relatively to their control strain Flinders Resistant Line (FRL). However, changes on transcript level related to serotonergic and glutamatergic signaling have only been sparsely studied in this model. The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine has fast-onset antidepressant properties, and recent data implicate serotonergic neurotransmission in ketamine's antidepressant-like activities in rodents. Here, we investigated the transcript levels of 40 genes involved in serotonergic and glutamatergic neurotransmission in FSL and FRL rats in response to a single dose of ketamine (15 mg/kg; 90 min prior to euthanization). Using real-time quantitative polymerase chain reaction, we studied the effect of ketamine in the hippocampus, whereas strain differences were investigated in both hippocampus and frontal cortex. The expression of genes involved in serotonergic and glutamatergic neurotransmission were unaffected by a single dose of ketamine in the hippocampus. Relative to FRL rats, FSL rats displayed enhanced hippocampal transcript levels of 5-ht2c, and P11, whereas the expression was reduced for 5-ht2a, Nr2a, and Mglur2. In the frontal cortex, we found higher transcript levels of 5-ht2cand Mglur2, whereas the expression of 5-ht2awas reduced in FSL rats. Thus, ketamine is not associated with hippocampal alterations in serotonergic or glutamatergic genes at 90 min after an antidepressant dose. Furthermore, FSL rats display serotonergic and glutamatergic abnormalities on gene expression level that partly may resemble findings in MDD patients.
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, Risskov, Denmark.
authors: Kristian Gaarn
authors: KG
authors: Du Jardin
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, Risskov, Denmark.
authors: Heidi Kaastrup
authors: HK
authors: Müller
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, Risskov, Denmark.|Lundbeck US LLC, 215 College Rd, Paramus, New Jersey.
authors: Connie
authors: C
authors: Sanchez
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, Risskov, Denmark.
authors: Gregers
authors: G
authors: Wegener
authors: Translational Neuropsychiatry Unit, Department of Clinical Medicine, Aarhus University, Skovagervej 2, Risskov, Denmark.
authors: Betina
authors: B
authors: Elfving
mesh_terms: D000818:Animals; D003865:Major Depressive Disorder / Q000235:genetics / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017470:Receptors, Glutamate / Q000235:genetics* / Q000378:metabolism; D011985:Receptors, Serotonin / Q000235:genetics* / Q000378:metabolism; D009435:Synaptic Transmission
chemical_list: D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D011985:Receptors, Serotonin; D007649:Ketamine
keywords: Flinders sensitive line rats; glutamate; ketamine; real-time polymerase chain reaction; serotonin