Neuropharmacist
Bluelighter
- Joined
- May 8, 2021
- Messages
- 20
Greetings!
I'm a neuropharmacologist studying the mechanisms of rapid-acting antidepressant treatments like ketamine. I've been reading bluelight occasionally for the past 15 years. Having recently started a Youtube-channel discussing various neuropharmacological topics, I thought there might be people interested in my content on the board. Please let me know if self-promotion is not allowed, I couldn't quickly find anything in the rules.
Let's get to the topic of the title: Ketamine and the disinhibition hypothesis. This is one of the most central hypotheses regarding the ability of subanesthetic doses of ketamine to produce therapeutic effects. Essentially, it states that at lower doses, ketamine preferentially binds to NMDA-receptors on GABAergic interneurons, leading to the disinhibition of excitatory neurons, facilitation of glutamate bursting and ultimately the activation of cellular signaling mechanisms that promote synaptic plasticity. High anesthetic doses, at least based on rodent studies and some human evidence, cause the opposite (e.g. inhibition and reduction of glutamate release) by blocking NMDARs all over. But I also believe that once the high doses start to come down, there may still exist a "sweet spot" where ketamine starts to disinhibit again. This may be similar to other anesthetics, which often cause emergence delirium and excitatory effects upon waking from the anesthesia.
I'd love to hear any thoughts on these putative mechanisms, as well as personal experiences from those suffering from depression and having experienced different ketamine doses.
I'm a neuropharmacologist studying the mechanisms of rapid-acting antidepressant treatments like ketamine. I've been reading bluelight occasionally for the past 15 years. Having recently started a Youtube-channel discussing various neuropharmacological topics, I thought there might be people interested in my content on the board. Please let me know if self-promotion is not allowed, I couldn't quickly find anything in the rules.
Let's get to the topic of the title: Ketamine and the disinhibition hypothesis. This is one of the most central hypotheses regarding the ability of subanesthetic doses of ketamine to produce therapeutic effects. Essentially, it states that at lower doses, ketamine preferentially binds to NMDA-receptors on GABAergic interneurons, leading to the disinhibition of excitatory neurons, facilitation of glutamate bursting and ultimately the activation of cellular signaling mechanisms that promote synaptic plasticity. High anesthetic doses, at least based on rodent studies and some human evidence, cause the opposite (e.g. inhibition and reduction of glutamate release) by blocking NMDARs all over. But I also believe that once the high doses start to come down, there may still exist a "sweet spot" where ketamine starts to disinhibit again. This may be similar to other anesthetics, which often cause emergence delirium and excitatory effects upon waking from the anesthesia.
I'd love to hear any thoughts on these putative mechanisms, as well as personal experiences from those suffering from depression and having experienced different ketamine doses.