Hippocampal Perineuronal Nets Are Required for the Sustained Antidepressant Effect of Ketamine.
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.



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.



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.



This suggests that parvalbumin interneuron function in the ventral hippocampus is essential for the sustained antidepressant effect of ketamine.
Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas.
Jennifer J
JJ
Donegan
Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas.
Daniel J
DJ
Lodge
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002810:Chondroitinases and Chondroitin Lyases / Q000378:metabolism; D003863:Depression / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology*; D046353:Immobility Response, Tonic / Q000187:drug effects; D007395:Interneurons / Q000187:drug effects*; D007649:Ketamine / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009415:Nerve Net / Q000187:drug effects*; D010320:Parvalbumins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D010320:Parvalbumins; D007649:Ketamine; D002810:Chondroitinases and Chondroitin Lyases
ketamine; perineuronal nets; ventral hippocampus