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The positive allosteric modulator at mGlu2 receptors, LY487379, reverses the effects of chronic stress-induced behavioral maladaptation and synaptic dysfunction in the adulthood
- Publication Year :
- 2019
-
Abstract
- Chronic stress induces maladaptive neural responses in several brain areas including hippocampus. It has been demonstrated that chronic stress exposure induced a downregulation of the putative presynaptic type 2 metabotropic glutamate (mGlu2) receptors, which would reduce the negative feedback role exerted by these receptors. The reduced availability of these receptors would enhance glutamate overflow in the hippocampus, supporting the hypothesis that hippocampal glutamatergic neurotransmission plays a key etiopathological determinant in stress-induced neuropsychiatric disorders. Since modulation of glutamatergic neurotransmission has been shown to represent an interesting pharmacological tool to treat psychiatric disorders, in the present study we have investigated the effects of the mGlu2 receptor positive allosteric modulator (PAM) LY487379. The rational bases of our study were: (a) chronic restraint stress (CRS) application in C57/BALB6 mouse induced a loss of resilience at the behavioral, biochemical, and electrophysiological level; (b) a superimposed familiar stressor (restraint) but not unfamiliar (i.e., forced swim stress) completely reversed the effects of CRS. Using the CRS model, in the present study we have investigated the effects of LY487379, an mGlu2 PAM, as well as a superimposed familiar stressor (acute restraint stress-ARS), on the immobility time at the tail suspension test and electrophysiological profile of glutamatergic transmission in the dentate gyrus (DG).
- Subjects :
- Male
Restraint, Physical
Allosteric modulator
hippocampus
Pyridines
Neurotransmission
Psychological Distress
Receptors, Metabotropic Glutamate
Synaptic Transmission
Mice
03 medical and health sciences
Cellular and Molecular Neuroscience
Glutamatergic
0302 clinical medicine
Animals
Medicine
Chronic stress
resilience
030304 developmental biology
Sulfonamides
0303 health sciences
business.industry
Mental Disorders
Dentate gyrus
chronic restraint stress
Glutamate receptor
Settore BIO/14
electrophysiology
Tail suspension test
Mice, Inbred C57BL
mGlu2 receptor
Metabotropic receptor
Dentate Gyrus
business
Neuroscience
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....21b1234520b06776a84e89ec6f9da8cf