Related Experiment Video
Updated: Mar 12, 2026
Author Spotlight: Studying Drug Impacts on Brain Signals Using Dual LFP Recording Protocol in Mice
Published on: February 16, 2024
Hippocampal Perineuronal Nets Are Required for the Sustained Antidepressant Effect of Ketamine
Jennifer J Donegan1, Daniel J Lodge1
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas.
Background:
N-methyl-D-aspartate receptor antagonists, like ketamine, produce a rapid-acting and long-lasting antidepressant effect. Although the mechanism is not completely understood, ketamine is thought to preferentially target N-methyl-D-aspartate receptors on fast-spiking parvalbumin-containing interneurons. The function of parvalbumin-containing interneurons is dependent on perineuronal nets, a specialized form of extracellular matrix that surrounds these cells.
Methods:
Chondroitinase was used to enzymatically degrade perineuronal nets surrounding parvalbumin-containing interneurons in the ventral hippocampus, a region that is involved in the antidepressant response to ketamine. Rats were tested on the forced swim test 30 minutes and 1 week after ketamine administration.
Results:
Thirty minutes after ketamine injection, both chondroitinase-treated and control animals had a decrease in immobility. One week later, however, the antidepressant-like response observed with ketamine was completely abolished in the chondroitinase-treated animals.
Conclusion:
This suggests that parvalbumin interneuron function in the ventral hippocampus is essential for the sustained antidepressant effect of ketamine.
