Modulation of defensive responses and anxiety-like behaviors by group I metabotropic glutamate receptors located in the dorsolateral periaqueductal gray

Lima, Vivian C.F.; Molchanov, M.L.; Aguiar, Daniele C.; Campos, Alline C.; Guimarães, Francisco Silveira

doi:10.1016/j.pnpbp.2007.08.006

Cited by 22 publications

(11 citation statements)

References 33 publications

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“…It is interesting to note that activation of these receptors also generates anxiogenic effects. For example, activation of group I metabotropic glutamate receptors in the dorsolateral periaqueductal gray facilitates defensive responses and anxiety-like behavior (Lima et al, 2008). It is well established that CRF is involved in stress and anxiety (Binder and Nemeroff, 2009; Hauger et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

Requirement of phospholipase C and protein kinase C in cholecystokinin‐mediated facilitation of NMDA channel function and anxiety‐like behavior

et al. 2011

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Whereas cholecystokinin (CCK) has long been known to exert anxiogenic effects in both animal anxiety models and humans, the underlying cellular and molecular mechanisms are ill-defined. CCK interacts with CCK-1 and CCK-2 receptors resulting in up-regulation of phospholipase C (PLC) and protein kinase C (PKC). However, the roles of PLC and PKC in CCK-mediated anxiogenic effects have not been determined. We have shown previously that CCK facilitates glutamate release in the hippocampus especially at the synapses formed by the perforant path and dentate gyrus granule cells via activations of PLC and PKC. Here we further demonstrated that CCK enhanced NMDA receptor function in dentate gyrus granule cells via activation of PLC and PKC pathway. At the single-channel level, CCK increased NMDA single-channel open probability and mean open time, reduced the mean close time and had no effects on the conductance of NMDA channels. Because elevation of glutamatergic functions results in anxiety, we explored the roles of PLC and PKC in CCK-induced anxiogenic actions using the Vogel Conflict Test (VCT). Our results from both pharmacological approach and knockout mice demonstrated that microinjection of CCK into the dentate gyrus concentration-dependently increased anxiety-like behavior via activation of PLC and PKC. Our results provide a novel unidentified signaling mechanism whereby CCK increases anxiety.

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Section: Discussionmentioning

confidence: 99%

Requirement of phospholipase C and protein kinase C in cholecystokinin‐mediated facilitation of NMDA channel function and anxiety‐like behavior

et al. 2011

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“…No anxiolytic activity on elevated plus maze test [151] Attenuation of stress-induced hyperthermia [151] Reduced vocalizations on ultrasonic vocalization procedure [151] 1-Aminoindan-1,5-dicarboxylic acid (AIDA) Anxiolytic activity on elevated plus maze test [152,153] Anxiolytic activity on Vogel conflict test [152,153] Anxiolytic activity on four-plate test [152] mGluR5 Antagonist…”

Section: Mglur2/3 Agonists In Stress-related Anxiety Disordersmentioning

confidence: 99%

“…Reduced stress-induced hyperthermia in mGlu5 knockout mice [154] No anxiolytic activity on elevated plus maze test [147] Anxiolytic activity on elevated plus maze test [155,156] Inhibition of fear-potentiated startle [139,147] Attenuation of freezing on contextual fear conditioning [147] Anxiolytic activity on Geller-Seifter conflict test [139,147] Anxiolytic activity on conditioned lick suppression test [150] Anxiolytic activity on Vogel conflict test [150,155] Anxiolytic activity on four-plate test [155] 2-Methyl-6-phenylethynylpyridine (MPEP) Attenuation of stress-induced hyperthermia [149,151,[157][158][159] No anxiolytic activity on elevated plus maze test [147] Anxiolytic activity on elevated plus maze test [151,[159][160][161][162] Anxiolytic activity on Vogel conflict test [138,148,150,153,160] Inhibition of fear-potentiated startle [154,163] Anxiolytic activity on four-plate test [160] Anxiolytic activity on Geller-Seifter conflict test [138,147] No anxiolytic activity on Geller-Seifter conflict test [159] Anxiolytic activity on conditioned lick suppression test [150] Anxiolytic activity on conditioned emotional response task [138] Decreased burying behaviour [159,162] Increased soci...…”

Section: -((2-methyl-4-thiazolyl)ethynyl)pyridine (Mtep)mentioning

confidence: 99%

Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists

et al. 2010

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Drugs acting at metabotropic glutamate receptors (mGluRs) are among the most promising agents under development for the treatment of psychiatric disorders. The research in this area is at a relatively early stage, as there are no drugs acting at mGluRs that have been approved for the treatment of any psychiatric disorder. However, in the areas of schizophrenia, anxiety disorders and mood disorders, research conducted in animal models appears to translate well into efficacy in human laboratory-based models of psychopathology and in preliminary clinical trials. Further, the genes coding for mGluRs are implicated in the risk for a growing number of psychiatric disorders. This review highlights the best studied mGluR strategies for psychiatry, based on human molecular genetics, studies in animal models and preliminary clinical trials. It describes the potential value of mGluR2 and mGluR5 agonists and positive allosteric modulators for the treatment of schizophrenia. It also reviews evidence that group II mGluR agonists and positive allosteric modulators as well as group I mGluR antagonists might also treat anxiety disorders and some forms of depression, while mGluR2 and group I mGluR antagonists (particularly mGluR5 antagonists) might have antidepressant properties. This review also links growing insights into the role of glutamate in the pathophysiology of these disorders to hypothesized mGluR-related treatment mechanisms.

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“…Metabotropic glutamate receptors (mGluR) in the dPAG could also play a role in anxiety modulation. For example, intra-dPAG administration of a group I and II mGluR agonist induced flight reactions, an effect attenuated by pretreatment with mGluR1 and mGluR5 antagonists (18). …”

Section: Classical Neurotransmitters the Pag And Defensive Behaviorsmentioning

confidence: 99%

Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

Fogaça

Lisboa

Aguiar

et al. 2012

Braz J Med Biol Res

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This paper presents an up-to-date review of the evidence indicating that atypical neurotransmitters such as nitric oxide (NO) and endocannabinoids (eCBs) play an important role in the regulation of aversive responses in the periaqueductal gray (PAG). Among the results supporting this role, several studies have shown that inhibitors of neuronal NO synthase or cannabinoid type 1 (CB1) receptor agonists cause clear anxiolytic responses when injected into this region. The nitrergic and eCB systems can regulate the activity of classical neurotransmitters such as glutamate and γ-aminobutyric acid (GABA) that control PAG activity. We propose that they exert a ‘fine-tuning’ regulatory control of defensive responses in this area. This control, however, is probably complex, which may explain the usually bell-shaped dose-response curves observed with drugs that act on NO- or CB1-mediated neurotransmission. Even if the mechanisms responsible for this complex interaction are still poorly understood, they are beginning to be recognized. For example, activation of transient receptor potential vanilloid type-1 channel (TRPV1) receptors by anandamide seems to counteract the anxiolytic effects induced by CB1 receptor activation caused by this compound. Further studies, however, are needed to identify other mechanisms responsible for this fine-tuning effect.

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Modulation of defensive responses and anxiety-like behaviors by group I metabotropic glutamate receptors located in the dorsolateral periaqueductal gray

Cited by 22 publications

References 33 publications

Requirement of phospholipase C and protein kinase C in cholecystokinin‐mediated facilitation of NMDA channel function and anxiety‐like behavior

Requirement of phospholipase C and protein kinase C in cholecystokinin‐mediated facilitation of NMDA channel function and anxiety‐like behavior

Potential Psychiatric Applications of Metabotropic Glutamate Receptor Agonists and Antagonists

Fine-tuning of defensive behaviors in the dorsal periaqueductal gray by atypical neurotransmitters

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