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Electroconvulsive Therapy01:30

Electroconvulsive Therapy

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Electroconvulsive therapy (ECT), or shock therapy, remains a critical biomedical intervention for severe, treatment-resistant depression. While its origins can be traced back to Hippocrates' observations that malaria-induced convulsions alleviated mental illness, modern ECT has evolved significantly from its earlier, more primitive applications. First introduced in 1938 by Ugo Cerletti and his colleagues, ECT involves inducing controlled seizures using electrical currents. In its early...
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Antidepressant Drugs: MAOIs and Other Agents01:23

Antidepressant Drugs: MAOIs and Other Agents

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Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
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Drugs Affecting Neurotransmitter Release or Uptake01:21

Drugs Affecting Neurotransmitter Release or Uptake

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Certain drugs can affect how neurotransmitters called catecholamines, are released or taken back up in the adrenergic neuron. They can have different effects on the body's sympathetic transmission. Reserpine, a natural compound found in the Rauwolfia shrub, blocks a transporter called vesicular monoamine transporter (VMAT), which leads to a buildup of catecholamines in the cell and reduces sympathetic transmission. Another drug called guanethidine works in multiple ways, including blocking...
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Antiepileptic Drugs: Potassium Channel Activators01:20

Antiepileptic Drugs: Potassium Channel Activators

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Ezocgabine or retigabine, an antiepileptic drug of remarkable efficacy, has revolutionized the management of seizures. It is a potassium channel activator, explicitly targeting the family of Q subtype potassium channels. It enhances the transmembrane potassium currents, regulating neuronal excitability. This action stabilizes the resting membrane potential, a pivotal factor in mitigating the hyperexcitability that characterizes epilepsy.
Ezogabine has gained approval as an adjunctive treatment...
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Sedatives and Hypnotics Drugs: Miscellaneous Agents01:17

Sedatives and Hypnotics Drugs: Miscellaneous Agents

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Sedatives and hypnotics encompass a wide range of substances, each with its unique mechanism of action, uses, and potential adverse effects.
Melatonin congeners like ramelteon (Rozerem) and tasimelteon (Hetlioz) selectively bind to melatonin receptors (MT1 and MT2) and thus mimic the actions of melatonin, a hormone that regulates sleep-wake cycles. Tasimelteon is primarily used for non-24-hour sleep-wake disorder, common in blind patients. They are also used to treat conditions like insomnia...
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Long-term Depression01:05

Long-term Depression

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Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
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Related Experiment Video

Updated: May 13, 2025

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins
09:07

Electroconvulsive Seizures in Rats and Fractionation of Their Hippocampi to Examine Seizure-induced Changes in Postsynaptic Density Proteins

Published on: August 15, 2017

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Enhanced ERK activity extends ketamine's antidepressant effects by augmenting synaptic plasticity.

Z Zack Ma1,2, Natalie J Guzikowski1,2, Ji-Woon Kim1,2

  • 1Department of Pharmacology, Vanderbilt University, Nashville, TN, USA.

Science (New York, N.Y.)
|May 8, 2025
PubMed
Summary

Sustaining ketamine

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Area of Science:

  • Neuroscience
  • Pharmacology
  • Molecular Psychiatry

Background:

  • Repeated ketamine treatment offers rapid antidepressant effects but causes side effects, necessitating strategies for sustained action from single doses.
  • Ketamine's antidepressant action is linked to synaptic potentiation at CA3-CA1 synapses, a key neural pathway.

Purpose of the Study:

  • To investigate methods for prolonging the antidepressant effects of ketamine by targeting intracellular signaling pathways.
  • To explore the role of dual-specificity phosphatases 6 (DUSP6) and extracellular signal-regulated kinase (ERK) in mediating ketamine's sustained effects.

Main Methods:

  • Pharmacological inhibition of DUSP6 to enhance ERK activity following ketamine administration.
  • Assessment of synaptic potentiation at CA3-CA1 synapses.
  • Evaluation of antidepressant-like behavioral effects in animal models.
  • Selective deletion of tropomyosin receptor kinase B (TrkB) in excitatory neurons to determine its role.

Main Results:

  • Inhibiting DUSP6 augmented ketamine-induced synaptic potentiation at CA3-CA1 synapses.
  • DUSP6 inhibition extended the antidepressant-like behavioral effects of ketamine for up to 2 months.
  • The effects of DUSP6 inhibition on synaptic and behavioral outcomes were dependent on TrkB signaling in excitatory neurons.

Conclusions:

  • Transiently increasing extracellular signal-regulated kinase (ERK) activity via DUSP6 inhibition can sustain ketamine's antidepressant effects.
  • Targeting downstream intracellular signaling, specifically TrkB-dependent pathways, offers a promising strategy for prolonging ketamine's therapeutic benefits.
  • This approach addresses the clinical need for sustained antidepressant action from single-dose ketamine administration.