Reduced metabotropic glutamate receptor 5 in the Flinders Sensitive Line of rats, an animal model of depression: An autoradiographic study

Abstract

Depression is a brain disorder and there is still only a partial understanding of its underlying pathophysiology. Antidepressant medications with a fast onset have not yet been developed. In addition to the monoaminergic systems, the brain glutaminergic system has been implicated in the etiology of depression. Animal studies of depression have gained importance because they permit a more invasive manipulation of the subjects than human studies. In the present study, we measured the densities of the brain regional metabotropic glutaminergic receptor 5 (mGluR5) in the Flinders Sensitive Line (FSL) rat model of depression and two groups of control rats, the Flinders Resistant Line (FRL) and Sprague Dawley (SPD), the parent strain for both the FSL and FRL rats. The FSL rats showed lower densities of mGluR5 in many brain regions compared to either the SPD and/or FRL rats. In addition, the densities in the FRL rats were larger than in the SPD rats, suggesting possible problems in using FRL rats as controls. The presented data suggest that mGluR5 is lower in animal models of depression which could be related to the cognitive and emotional dysfunctions in the FSL rat model of depression and could be relevant to a better understanding of depression in humans. Keywords

Mitochondrial plasticity of the hippocampus in a genetic rat model of depression after antidepressant treatment

“…They also observed dysfunctional astrocytic glutamate regulation in FSL rats (Gomez‐Galan et al,2012). In addition, reduced expression and function of mGlu2/3 (Matrisciano et al,2008) and mGluR5 (Kovacevic et al,2012) metabotropic glutamate receptors found in the hippocampus of FSL rats, and presynaptic mGluR autoreceptors actively inhibit glutamate release (Glaum and Miller,1993). All of these indicated FSL rats have increased glutaminergic neurotransmission.…”

Metabotropic Glutamate Receptor 5 and Glutamate Involvement in Major Depressive Disorder: A Multimodal Imaging Study

“…However, the relationship between mGluR5 changes and depressive-like behavior is complex and not fully understood. Animal models of depression showed reductions in mGluR5 protein and density in various brain regions (14, 15). Similarly, mGluR5 knockout mice exhibited depressive-like behavior (16) and chronic, but not acute, antidepressant treatment increased mGluR5 expression (17), raising the possibility that therapeutic effects might be mediated by mGluR5 regulation.…”

Metabotropic glutamate receptor mGluR2/3 and mGluR5 binding in the anterior cingulate cortex in psychotic and nonpsychotic depression, bipolar disorder and schizophrenia: implications for novel mGluR-based therapeutics

“…11 In addition to their therapeutic potential, mGluRs are also implicated in the pathophysiology of these disorders. For example, numerous animal studies demonstrate that selected mGluRs are affected in animal models of depression, 14,15 and knockout animals display psychotic pheno typic behaviours. 11,13 From these studies, it is becoming increasingly clear that there may be opposing actions of the glutamatergic system in these disorders, particularly as mGluR2/3 and mGluR5 blockade appear to be beneficial for the treatment of depression, while potentiation of these receptors has preclinical efficacy for the treatment of psychosis.…”