mGlu2 and mGlu3 Negative Allosteric Modulators Divergently Enhance Thalamocortical Transmission and Exert Rapid Antidepressant-like Effects

Publication date: Available online 14 November 2019Source: NeuronAuthor(s): Max E. Joffe, Chiaki I. Santiago, Kendra H. Oliver, James Maksymetz, Nicholas A. Harris, Julie L. Engers, Craig W. Lindsley, Danny G. Winder, P. Jeffrey ConnSummaryNon-selective antagonists of metabotropic glutamate receptor subtypes 2 (mGlu2) and 3 (mGlu3) exert rapid antidepressant-like effects by enhancing prefrontal cortex (PFC) glutamate transmission; however, the receptor subtype contributions and underlying mechanisms remain unclear. Here, we leveraged newly developed negative allosteric modulators (NAMs), transgenic mice, and viral-assisted optogenetics to test the hypothesis that selective inhibition of mGlu2 or mGlu3 potentiates PFC excitatory transmission and confers antidepressant efficacy in preclinical models. We found that systemic treatment with an mGlu2 or mGlu3 NAM rapidly activated biophysically unique PFC pyramidal cell ensembles. Mechanistic studies revealed that mGlu2 and mGlu3 NAMs enhance thalamocortical transmission and inhibit long-term depression by mechanistically distinct presynaptic and postsynaptic actions. Consistent with these actions, systemic treatment with either NAM decreased passive coping and reversed anhedonia in two independent chronic stress models, suggesting that both mGlu2 and mGlu3 NAMs induce antidepressant-like effects through related but divergent mechanisms of action.Graphical Abstract
Source: Neuron - Category: Neuroscience Source Type: research

Related Links:

Conclusion: Experiencing defibrillator shocks was associated with psychological distress in ICD recipients; the relationship was fully mediated by ICD-related concerns and perceived control. These results suggest that clinicians should routinely assess ICD-related concerns and perceived control in patients with ICD. Research is needed to develop and test interventions to decrease emotional distress related to the ICD shock experience.
Source: Journal of Cardiovascular Nursing - Category: Nursing Tags: ARTICLES: Cardiovascular Disease Source Type: research
Authors: Fang L, Xu Z, Lu J, Hong L, Qiao S, Liu L, An J Abstract Hypothyroidism is associated with profound left ventricular dysfunction. Triiodothyronine (T3) supplementation may improve cardiac function after ischemic reperfusion (I/R) injury. In the present study, the effect of T3 on major calcium cycling proteins and high-energy phosphate content during I/R was evaluated. Isolated perfused rat hearts were divided into 5 groups: Sham Control (Sham, n=10), Control (n=8), T3 10 nM (T3-10, n=10), T3 25 nM (T3-25, n=10) and T3 50 nM (T3-50, n=10). T3 was administrated for 60 min before 30 min of ischemia and 120 mi...
Source: Experimental and Therapeutic Medicine - Category: General Medicine Tags: Exp Ther Med Source Type: research
Conclusions: Knowledge of HIV status, be it positive or negative, was significantly associated with a decrease in depressive symptoms in 2 FSW populations. The expansion of HIV testing programs may have mental health benefits for FSWs.
Source: JAIDS Journal of Acquired Immune Deficiency Syndromes - Category: Infectious Diseases Tags: Prevention Research Source Type: research
DiscussionThese preliminary results suggest that even if patients believe that they have reduced cognition caused by their vestibular deficits, it remains challenging to demonstrate the effects using simple (standard) objective cognitive measures. We discuss the mismatch in results in terms of cognitive specificity, complexity and compensation. We propose that the objective measures may more likely show effects if combined with a dual task, or by performing complex imagery tasks, adding strain to cognitive resources.
Source: Neurophysiologie Clinique - Category: Neuroscience Source Type: research
DiscussionThe hypothesis of a depressed sensory transmission during continued skin compression was supported by our microneurographic recordings showing adaptation/suppression of tactile fibres discharge during continuous pressure applied to the mechanoreceptors. Finally, the hypothesis that large sways during standing correspond to a self-generated functional behaviour to release skin compression is supported by cortical source and EMG analyses showing respectively that large sways were preceded by activation of cortical areas known to be engaged in motor planning (supplementary motor area and dorsolateral prefrontal cort...
Source: Neurophysiologie Clinique - Category: Neuroscience Source Type: research
The novel drug SAGE-217 did not meet its primary outcome of reduction in depression scores at day 15 in the phase 3 MOUNTAIN trial, but additional analyses show"supportive" data, researchers say.Medscape Medical News
Source: Medscape Psychiatry Headlines - Category: Psychiatry Tags: Psychiatry News Source Type: news
ConclusionThe findings from the current study contribute to the resources to better oversee projects to upgrade health sciences students' self-esteem, some short term courses (i.e. English, personality development and motivation) are requested to boost the academic career and confidence by lifting self-esteem; it indirectly helps to better academic performance. Students also need special counseling for how to deal with stress, anxiety and depression.
Source: Saudi Journal of Biological Sciences - Category: Biology Source Type: research
AbstractWe explored the association between HIV-related stigma and experiences of intimate partner violence (IPV) and depression with viral load suppression, and medication and visit adherence in postpartum women receiving lifelong antiretroviral therapy (ART) (N  = 200). We administered a cross-sectional survey to 200 women with HIV at 12 months postpartum who were enrolled in the MOTIVATE trial. The MOTIVATE study is a cluster-randomized trial evaluating the impact of community mentor mothers and text messaging on PMTCT outcomes in southwestern Kenya. Simple and multivariable logistic regression analys...
Source: AIDS and Behavior - Category: Infectious Diseases Source Type: research
AbstractStudies have documented how levels and change in depression correspond to ART non-adherence. However, few studies have examined how levels of and change in adherence may relate to levels of and change in depression, although one might expect mental health to be related to physical health and how successful one is in managing disease. To assess the bidirectional nature of the association between these two constructs, we examined data from a prospective trial of an ART adherence intervention in Uganda that followed 143 participants over 20  months. Adherence was measured using electronic monitoring caps; non-adh...
Source: AIDS and Behavior - Category: Infectious Diseases Source Type: research
We examined the association of prescription NSAIDs to depression among adults with inflammatory chronic conditions in a nationally representative sample of the US non-institutionalized civilian population. We used a retrospective cross-sectional design. Data on 10,713 adults with inflammatory chronic conditions were derived from 2015 Medical Expenditure Panel Survey (MEPS). The dependent variable was the presence or absence of depression and the key independent variable was prescription NSAIDs use. Logistic regression models were used to examine the adjusted associations of prescription NSAIDs to depression. In these regre...
Source: Psychiatric Quarterly - Category: Psychiatry Source Type: research
More News: Brain | Depression | Neurology | Neuroscience | Opthalmology | Study