The Action of Antidepressants on the Glutamate System: Regulation of Glutamate Release and Glutamate Receptors

Musazzi, Laura; Treccani, Giulia; Mallei, Alessandra; Popoli, Maurizio

doi:10.1016/j.biopsych.2012.11.009

Cited by 159 publications

(109 citation statements)

References 97 publications

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“…These compounds may have both pre-and postsynaptic effects (Musazzi et al, 2013) and depending on the compound, may show extremely rapid effects (Krystal et al, 2013). These will be the subjects of a future study.…”

Section: Discussionmentioning

confidence: 98%

Lateral Diffusion of Gαs in the Plasma Membrane Is Decreased after Chronic but not Acute Antidepressant Treatment: Role of Lipid Raft and Non-Raft Membrane Microdomains

Czysz

Schappi

Rasenick

2014

Neuropsychopharmacol

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GPCR signaling is modified both in major depressive disorder and by chronic antidepressant treatment. Endogenous Ga s redistributes from raft-to nonraft-membrane fractions after chronic antidepressant treatment. Modification of G protein anchoring may participate in this process. Regulation of Ga s signaling by antidepressants was studied using fluorescence recovery after photobleaching (FRAP) of GFP-Ga s . Here we find that extended antidepressant treatment both increases the half-time of maximum recovery of GFP-Ga s and decreases the extent of recovery. Furthermore, this effect parallels the movement of Ga s out of lipid rafts as determined by cold detergent membrane extraction with respect to both dose and duration of drug treatment. This effect was observed for several classes of compounds with antidepressant activity, whereas closely related molecules lacking antidepressant activity (eg, R-citalopram) did not produce the effect. These results are consistent with previously observed antidepressant-induced translocation of Ga s , but also suggest an alternate membrane attachment site for this G protein. Furthermore, FRAP analysis provides the possibility of a relatively high-throughput screening tool for compounds with putative antidepressant activity.

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Section: Discussionmentioning

confidence: 98%

Lateral Diffusion of Gαs in the Plasma Membrane Is Decreased after Chronic but not Acute Antidepressant Treatment: Role of Lipid Raft and Non-Raft Membrane Microdomains

Czysz

Schappi

Rasenick

2014

Neuropsychopharmacol

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“…Abnormalities in these dopaminergic and glutamatergic systems have been observed in numerous neuropsychiatric disorders, including Parkinson's disease (Griffith et al, 2008;Loane and Politis, 2011;Pavese et al, 2011), depression (Musazzi et al, 2012;Treadway and Zald, 2011), drug addiction (Martinez et al, 2009;Yang et al, 2009;Yucel et al, 2007), and schizophrenia (de la Fuente-Sandoval et al, 2013a,b;de la Fuente-Sandoval et al, 2011;Kegeles et al, 2010). The classical model of the basal ganglia developed in the 1980s (Obeso and Lanciego, 2011) predicts that loss of striatal dopamine will decrease extracellular levels of glutamate in the striatum and cortex (Albin et al, 1989(Albin et al, , 1995Jones, 2012).…”

Section: Introductionmentioning

confidence: 99%

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

Caravaggio

Nakajima

Plitman

et al. 2016

Progress in Neuro-Psychopharmacology and Biological Psychiatry

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Understanding the interplay between the neurotransmitters dopamine and glutamate in the striatum has become the highlight of several theories of neuropsychiatric illnesses, such as schizophrenia. Using in vivo brain imaging in humans, alterations in dopamine and glutamate concentrations have been observed in several neuropsychiatric disorders. However, it is unclear a priori how alterations in striatal dopamine should modulate glutamate concentrations in the basal ganglia. In this selective mini-review, we examine the consequence of reducing striatal dopamine functioning on glutamate concentrations in the striatum and cortex; regions of interest heavily examined in the human brain imaging studies. We examine the predictions of the classical model of the basal ganglia, and contrast it with findings in humans and animals. The review concludes that chronic dopamine depletion (>4 months) produces decreases in striatal glutamate levels which are consistent with the classical model of the basal ganglia. However, acute alterations in striatal dopamine functioning, specifically at the D2 receptors, may produce opposite affects. This has important implications for models of the basal ganglia and theorizing about neurochemical alterations in neuropsychiatric diseases. Moreover, these findings may help guide a priori hypotheses for 1H-MRS studies measuring glutamate changes given alterations in dopaminergic functioning in humans.

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“…Furthermore, repeated ketamine infusion also has a sustained antidepressant effect, with no clinically signifi cant psychotomimetic effects [113] . In contrast to most approved antidepressants which target the monoaminergic system, ketamine has a direct and rapid effect on the glutamatergic system and synaptic plasticity [47] . Ketamine rapidly increases the expression of synaptic proteins and the number of excitatory spine synapses in the PFC [50,114,115] .…”

Section: Ketamine Has Rapid-onset Antidepressant Effi Cacymentioning

confidence: 99%

Section: Dysfunctional Neural Plasticity In Depressionmentioning

confidence: 99%

“…The underlying mechanism is associated with a marked increase in depolarization-evoked glutamate release in the PFC, which can be mitigated by monoaminebased antidepressants [44][45][46] . Moreover, antidepressants reduce the release of glutamate, possibly by decreasing phospho-activation of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) [47] .Antidepressants can enhance structural plasticity and neurogenesis. A few days (~5 days) of fluoxetine administration increases synaptic density in the hippocampal CA1 pyramidal cell layer, and 14 days of treatment has similar effects in the CA3 pyramidal cell layer [48] .…”

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confidence: 99%

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Rapid-onset antidepressant efficacy of glutamatergic system modulators: The neural plasticity hypothesis of depression

et al. 2014

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Depression is a devastating psychiatric disorder widely attributed to defi cient monoaminergic signaling in the central nervous system. However, most clinical antidepressants enhance monoaminergic neurotransmission with little delay but require 4−8 weeks to reach therapeutic efficacy, a paradox suggesting that the monoaminergic hypothesis of depression is an oversimplifi cation. In contrast to the antidepressants targeting the monoaminergic system, a single dose of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine produces rapid (within 2 h) and sustained (over 7 days) antidepressant effi cacy in treatment-resistant patients. Glutamatergic transmission mediated by NMDARs is critical for experience-dependent synaptic plasticity and learning, processes that can be modifi ed indirectly by the monoaminergic system. To better understand the mechanisms of action of the new antidepressants like ketamine, we review and compare the monoaminergic and glutamatergic antidepressants, with emphasis on neural plasticity. The pathogenesis of depression may involve maladaptive neural plasticity in glutamatergic circuits that may serve as a new class of targets to produce rapid antidepressant effects.Keywords: depression; stress; neural plasticity; glutamatergic transmission; monoamine-based antidepressant; ketamine IntroductionDepression is a common psychiatric disorder, with prevalence rates of 19% in Beirut and 16.2% in the UnitedStates [1] . Depression is also one of the leading causes of severe mental disability, suicide, and socioeconomic burden, and its diagnosis sometimes relies on selfreported symptoms in the major depressive inventory [2,3] .The pathogenesis of depression is still not clear, and currently available antidepressants are far from satisfactory.Most antidepressants target the monoaminergic system [4] ; however, 30%-40% of patients are resistant to monoaminebased antidepressants (remittance rates of 13% to 36.8% with citalopram [5] ), and a clinically significant reduction of depressive symptoms in responders usually requires 4−8 weeks of daily treatment [6] . These limitations result in a large proportion of patients at high risk of suicide even after diagnosis. Thus, it is necessary to search for new antidepressants outside the monoaminergic system. R ecent clinical studies have demonstrated that a single dose of the N-methyl-D-aspartate receptor (NMDAR) antagonist ketamine has rapid antidepressant efficacy within 2 h that can be sustained for over 7 days in patients with treatment-resistant depression [7,8] . This finding suggests that depression could be directly associated with defi cits in glutamatergic synaptic transmission and plasticity. The monoaminergic hypothesis of depression, based on the efficacy of antidepressants that enhance monoaminergic transmission and signaling, has dominated the field of depression research for nearly half a century.However, the primacy of monoaminergic dysfunction in depression is inconsistent with the delay between enhancement of synaptic monoamines confer...

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The Action of Antidepressants on the Glutamate System: Regulation of Glutamate Release and Glutamate Receptors

Cited by 159 publications

References 97 publications

Lateral Diffusion of Gαs in the Plasma Membrane Is Decreased after Chronic but not Acute Antidepressant Treatment: Role of Lipid Raft and Non-Raft Membrane Microdomains

Lateral Diffusion of Gαs in the Plasma Membrane Is Decreased after Chronic but not Acute Antidepressant Treatment: Role of Lipid Raft and Non-Raft Membrane Microdomains

The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

Rapid-onset antidepressant efficacy of glutamatergic system modulators: The neural plasticity hypothesis of depression

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