Antidepressant-like actions of an AMPA receptor potentiator (LY392098)

Li, Xia; Tizzano, Joseph P.; Griffey, Kelly I.; Clay, Michael P.; Lindstrom, Terry D.; Skolnick, Phil

doi:10.1016/s0028-3908(00)00194-5

Cited by 209 publications

(124 citation statements)

References 35 publications

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Section: Targeting Amparsmentioning

confidence: 99%

“…GluR1 phosphorylation is transiently increased by stress, possibly contributing to the stress-induced facilitation of memory [122] . In addition, the AMPAR potentiators LY392098 and LY451646 have antidepressant effects in the FST and TST [123][124][125] .Enhanced phosphorylation of GluR1 has been detected following fluoxetine, imipramine, and ketamine treatment, and ketamine rapidly increases postsynaptic AMPAR expression [103,104,115] . Moreover, the onset of ketamine effects requires AMPARs, as the antidepressant-like behaviors are attenuated by pre-treatment with the AMPAR antagonist NBQX in mouse models of depression [116] .…”

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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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Section: Targeting Amparsmentioning

confidence: 99%

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confidence: 99%

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

et al. 2014

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“…In vitro, biarylsulfonamides increase AMPA currents in isolated hippocampal and Purkinje neurons (Gates et al, 2001) and AMPA receptor-mediated synaptic inputs in frontal cortex (fCTX) pyramidal neurons (Quirk and Nisenbaum, 2002). In vivo they are active in rodent models of memory and cognition (Quirk and Nisenbaum, 2002) and display an antidepressant profile in behavioral models (Li et al, 2001). They have also been shown to increase brain-derived neurotrophic factor (BDNF) both in vitro and in vivo (O'Neill et al, 2004).…”

Section: Introductionmentioning

confidence: 99%

AMPA Receptor Potentiation can Prevent Ethanol-Induced Intoxication

Jones

Messenger

O’Neill

et al. 2007

Neuropsychopharmacol

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We present a substantial series of behavioral and imaging experiments, which demonstrate, for the first time, that increasing AMPA receptor-mediated neurotransmission via administration of potent and selective biarylsulfonamide AMPA potentiators LY404187 and LY451395 reverses the central effects of an acutely intoxicating dose of ethanol in the rat. Using pharmacological magnetic resonance imaging (phMRI), we observed that LY404187 attenuated ethanol-induced reductions in blood oxygenation level dependent (BOLD) in the anesthetized rat brain. A similar attenuation was apparent when measuring local cerebral glucose utilization (LCGU) via C 14 -2-deoxyglucose autoradiography in freely moving conscious rats. Both LY404187 and LY451395 significantly and dose-dependently reversed ethanol-induced deficits in both motor coordination and disruptions in an operant task where animals were trained to press a lever for food reward. Both prophylactic and acute intervention treatment with LY404187 reversed ethanol-induced deficits in motor coordination. Given that LY451395 and related AMPA receptor potentiators/ampakines are tolerated in both healthy volunteers and elderly patients, these data suggest that such compounds may form a potential management strategy for acute alcohol intoxication.

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“…We appreciate the author's excellent perspectives and want to raise a hypothesis regarding the mechanisms of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonists exerting fast-acting antidepressant effects.A series of studies have demonstrated that AMPA receptor agonist such as LY392098 show fast-acting antidepressant effects in the rodent animal models (Li et al 2001). Moreover, Maeng et al (2008) have observed that pretreatment with AMPA receptor antagonist NBQX can significantly reduce the ketamine's antidepressant effects.…”

mentioning

confidence: 99%

“…A series of studies have demonstrated that AMPA receptor agonist such as LY392098 show fast-acting antidepressant effects in the rodent animal models (Li et al 2001). Moreover, Maeng et al (2008) have observed that pretreatment with AMPA receptor antagonist NBQX can significantly reduce the ketamine's antidepressant effects.…”

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confidence: 99%

Is mTOR involved in the mechanisms of the fast-acting antidepressant effects of AMPA receptor agonists?

Liu

Shen

2012

Amino Acids

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We read with great interest the article ''The involvement of AMPA-ERK1/2-BDNF pathway in the mechanism of new antidepressant action of prokinetic meranzin hydrate'', in which the authors concluded that AMPA receptors were involved in the mechanism of the antidepressant effects of prokinetic meranzin hydrate (Xie et al. 2012). We appreciate the author's excellent perspectives and want to raise a hypothesis regarding the mechanisms of a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor agonists exerting fast-acting antidepressant effects.A series of studies have demonstrated that AMPA receptor agonist such as LY392098 show fast-acting antidepressant effects in the rodent animal models (Li et al. 2001). Moreover, Maeng et al. (2008) have observed that pretreatment with AMPA receptor antagonist NBQX can significantly reduce the ketamine's antidepressant effects. The ketamine-induced increase in glutamate release preferentially favors AMPA receptors over NMDA receptors because the latter have been occupied by ketamine, therefore the net antidepressant effect of ketamine is increased by glutamatergic throughput (Machado-Vieira et al. 2009). Collectively, these studies have indicated that AMPA receptors are essential for ketamine to exert its antidepressant effects (Duman and Voleti 2012). Recently, an innovative study conducted by Li et al. (2010) showing that mammalian target of rapamycin (mTOR) activation in prefrontal cortex is involved in the ketamine exerting fastacting antidepressant effects. Thus, we hypothesized that AMPA receptor agonists exerting their antidepressant effects are potentially via up-regulating Akt and ultimately activating mTOR. Future studies are needed to verify the hypothesis and enrich this field knowledge. Conflict of interest

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Antidepressant-like actions of an AMPA receptor potentiator (LY392098)

Cited by 209 publications

References 35 publications

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

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

AMPA Receptor Potentiation can Prevent Ethanol-Induced Intoxication

Is mTOR involved in the mechanisms of the fast-acting antidepressant effects of AMPA receptor agonists?

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