Emerging treatment mechanisms for depression: focus on glutamate and synaptic plasticity
Drug discovery today, 2016•Elsevier
Highlights•Stress and depression are characterized by loss of synapses in prefrontal
cortex.•Rapid acting antidepressants increase synaptic contacts in prefrontal cortex.•NMDA
antagonists, notably ketamine are a new class of rapid acting antidepressant.•A burst of
glutamate underlies the rapid actions of ketamine.•Glutamate transmission offers novel sites
for therapeutic intervention.Major depression is a chronic and debilitating illness that effects
approximately 1 in 5 people, but currently available treatments are limited by low rates of …
cortex.•Rapid acting antidepressants increase synaptic contacts in prefrontal cortex.•NMDA
antagonists, notably ketamine are a new class of rapid acting antidepressant.•A burst of
glutamate underlies the rapid actions of ketamine.•Glutamate transmission offers novel sites
for therapeutic intervention.Major depression is a chronic and debilitating illness that effects
approximately 1 in 5 people, but currently available treatments are limited by low rates of …
Highlights
- Stress and depression are characterized by loss of synapses in prefrontal cortex.
- Rapid acting antidepressants increase synaptic contacts in prefrontal cortex.
- NMDA antagonists, notably ketamine are a new class of rapid acting antidepressant.
- A burst of glutamate underlies the rapid actions of ketamine.
- Glutamate transmission offers novel sites for therapeutic intervention.
Major depression is a chronic and debilitating illness that effects approximately 1 in 5 people, but currently available treatments are limited by low rates of efficacy, therapeutic time lag, and undesirable side effects. Recent efforts have been directed towards investigating rapid-acting agents that reverse the behavioral and neuronal deficits of chronic stress and depression, notably the glutamate NMDA receptor antagonist ketamine. The cellular mechanisms underlying the rapid antidepressant actions of ketamine and related agents are discussed, as well as novel, selective glutamatergic receptor targets that are safer and have fewer side effects.
Elsevier