Effects of ketamine and other rapidly acting antidepressants on hippocampal excitatory and inhibitory transmission.

Effects of ketamine and other rapidly acting antidepressants on hippocampal excitatory and inhibitory transmission.
Adv Pharmacol. 2020;89:3-41
Authors: Widman AJ, McMahon LL
Abstract
A single sub-anesthetic intravascular dose of the use-dependent NMDAR antagonist, ketamine, improves mood in patients with treatment resistant depression within hours that can last for days, creating an entirely new treatment strategy for the most seriously ill patients. However, the psychomimetic effects and abuse potential of ketamine require that new therapies be developed that maintain the rapid antidepressant effects of ketamine without the unwanted side effects. This necessitates a detailed understanding of what cellular and synaptic mechanisms are immediately activated once ketamine reaches the brain that triggers the needed changes to elicit the improved behavior. Intense research has centered on the effects of ketamine, and the other rapidly acting antidepressants, on excitatory and inhibitory circuits in hippocampus and medial prefrontal cortex to determine common mechanisms, including key modifications in synaptic transmission and the precise location of the NMDARs that mediate the rapid and sustained antidepressant response. We review data comparing the effects of ketamine with other NMDAR receptor modulators and the muscarinic M1 acetylcholine receptor antagonist, scopolamine, together with evidence supporting the disinhibition hypothesis a...

Source: Advances in Pharmacology - July 4, 2020 Category: Drugs & Pharmacology Authors: Widman AJ, McMahon LL Tags: Adv Pharmacol Source Type: research