Adolescent administration of ketamine impairs excitatory synapse formation onto parvalbumin-positive GABAergic interneurons in mouse prefrontal cortex.
Biochemical and biophysical research communications September 17, 2024 Jia-Wei Zhang, Hai-Qian Zhou, Zhen Zhu et al. 7 citations
Adolescent ketamine abuse causes lasting deficits in cognition and social behavior by reducing excitatory synapses on parvalbumin (PV) inhibitory neurons in the medial prefrontal cortex (mPFC), while sparing excitatory pyramidal neurons. In rats given sub-chronic ketamine during early adolescence, the density of these synapses remained lower into adulthood, leading to hyperexcitability, impaired working memory, and reduced social interaction compared to controls. Bioinformatic analysis revealed decreased expression of a gene co-expression module (M1) critical for inhibitory neuron synapse development. The findings suggest that adolescent ketamine exposure irreversibly disrupts synaptic development, pointing to potential therapeutic targets.