The Emerging Role of Metabotropic Glutamate Receptors in the Pathophysiology of Chronic Stress-Related Disorders
نویسندگان
چکیده
Chronic stress-related psychiatric conditions such as anxiety, depression, and alcohol abuse are an enormous public health concern. The etiology of these pathologies is complex, with psychosocial stressors being among the most frequently discussed risk factors. The brain glutamatergic neurotransmitter system has often been found involved in behaviors and pathophysiologies resulting from acute stress and fear. Despite this, relatively little is known about the role of glutamatergic system components in chronic psychosocial stress, neither in rodents nor in humans. Recently, drug discovery efforts at the metabotropic receptor subtypes of the glutamatergic system (mGlu1-8 receptors) led to the identification of pharmacological tools with emerging potential in psychiatric conditions. But again, the contribution of individual mGlu subtypes to the manifestation of physiological, molecular, and behavioral consequences of chronic psychosocial stress remains still largely unaddressed. The current review will describe animal models typically used to analyze acute and particularly chronic stress conditions, including models of psychosocial stress, and there we will discuss the emerging roles for mGlu receptor subtypes. Indeed, accumulating evidence indicates relevance and potential therapeutic usefulness of mGlu2/3 ligands and mGlu5 receptor antagonists in chronic stress-related disorders. In addition, a role for further mechanisms, e.g. mGlu7-selective compounds, is beginning to emerge. These mechanisms are important to be analyzed in chronic psychosocial stress paradigms, e.g. in the chronic subordinate colony housing (CSC) model. We summarize the early results and discuss necessary future investigations, especially for mGlu5 and mGlu7 receptor blockers, which might serve to suggest improved therapeutic strategies to treat stress-related disorders.
منابع مشابه
Ionotropic Glutamate Receptors and their Role in Neurological Diseases
Glutamate is extensively and relatively uniformly distributed in the central nervous system (CNS) and its effects mediated by two distinct groups of receptors including Ionotropic and metabotropic glutamate receptors. Concentration of glutamate in the nervous system is much higher than in other tissues. Glutamate receptors play an important role in synaptic transmission, neural plasticity and n...
متن کاملMetabotropic glutamate receptors and their ligands applications in neurological and psychiatric disorders
Metabotropic glutamate receptors (mGluRs) consist of a large family of G-protein coupled receptors that are critical for regulating normal neuronal function in the central nervous system. The wide distribution and diverse physiological roles of various mGluR subtypes make them highly attractive targets for the treatment of a number of neurological and psychiatric disorders. The discovery of ...
متن کامل(S)- 3,5-Dihydroxyphenylglycine )an agonist for group I metabotropic glutamate receptors( induced synaptic potentiation at excitatory synapses on fast spiking GABAergic cells in visual cortex
Introduction: (S)- 3,5-Dihydroxyphenylglycine (DHPG) is an agonist for group I metabotropic glutamate receptors. DHPG-induced synaptic depression of excitatory synapses on hippocampal pyramidal neurons is well known model for synaptic plasticity studies. The aim of the present study was to examine the effects of DHPG superfusion on excitatory synapses on pyramidal and fast-spiking GABAergic cel...
متن کاملP6: Metabotropic Glutamate Receptor-Dependent Role in the Formation of Long-Term Potentiation
Long-term potentiation (LTP) is a reflection of synaptic plasticity that induced by specific patterns of synaptic activity and has an important role in learning and memory. The first clue of the potential role of glutamate receptors in LTP was in 1991 with the observation that the mGluR agonists 1-amino-1, 3-cyclopentanedicarboxylic acid (ACPD), increased LTP. Studies have shown that ACPD induc...
متن کامل