TY - JOUR
T1 - Gene expression related to serotonergic and glutamatergic neurotransmission is altered in the Flinders Sensitive Line rat model of depression
T2 - Effect of ketamine
AU - du Jardin, Kristian Gaarn
AU - Müller, Heidi Kaastrup
AU - Sanchez, Connie
AU - Wegener, Gregers
AU - Elfving, Betina
N1 - © 2016 Wiley Periodicals, Inc.
PY - 2017/1
Y1 - 2017/1
N2 - 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-ht
2c, and P11, whereas the expression was reduced for 5-ht
2a, Nr2a, and Mglur2. In the frontal cortex, we found higher transcript levels of 5-ht
2c and Mglur2, whereas the expression of 5-ht
2a was 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.
AB - 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-ht
2c, and P11, whereas the expression was reduced for 5-ht
2a, Nr2a, and Mglur2. In the frontal cortex, we found higher transcript levels of 5-ht
2c and Mglur2, whereas the expression of 5-ht
2a was 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.
KW - Flinders sensitive line rats
KW - glutamate
KW - ketamine
KW - real-time polymerase chain reaction
KW - serotonin
UR - http://www.scopus.com/inward/record.url?scp=84996656650&partnerID=8YFLogxK
U2 - 10.1002/syn.21940
DO - 10.1002/syn.21940
M3 - Journal article
C2 - 27589698
SN - 0887-4476
VL - 71
SP - 37
EP - 45
JO - Synapse
JF - Synapse
IS - 1
ER -