AI Article Synopsis
- Ketamine acts as an NMDA receptor antagonist, leading to psychedelic effects by distorting sensory input and altering brain activity through several interconnected mechanisms.
- It inhibits short-term potentiation (STP) and long-term potentiation (LTP) in different ways, which can affect memory and sensory processing.
- The findings suggest that ketamine's psychedelic properties may be linked to its ability to inhibit STP and potentially impact working memory, emphasizing its unique pharmacological profile.
Article Abstract
Ketamine, a channel blocking NMDA receptor antagonist, is used off-label for its psychedelic effects, which may arise from a combination of several inter-related actions. Firstly, reductions of the contribution of NMDA receptors to afferent information from external and internal sensory inputs may distort sensations and their processing in higher brain centres. Secondly, reductions of NMDA receptor-mediated excitation of GABAergic interneurons can result in glutamatergic overactivity. Thirdly, limbic cortical disinhibition may indirectly enhance dopaminergic and serotonergic activity. Fourthly, inhibition of NMDA receptor mediated synaptic plasticity, such as short-term potentiation (STP) and long-term potentiation (LTP), could lead to distorted memories. Here, for the first time, we compared quantitatively the effects of ketamine on STP and LTP. We report that ketamine inhibits STP in a double sigmoidal fashion with low (40 nM) and high (5.6 μM) IC values. In contrast, ketamine inhibits LTP in a single sigmoidal manner (IC value ∼ 15 μM). A GluN2D-subunit preferring NMDA receptor antagonist, UBP145, has a similar pharmacological profile. We propose that the psychedelic effects of ketamine may involve the inhibition of STP and, potentially, associated forms of working memory. This article is part of the Special Issue entitled 'Psychedelics: New Doors, Altered Perceptions'.
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| http://dx.doi.org/10.1016/j.neuropharm.2018.06.008 | DOI Listing |
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