Ketamine exposure in adult mice leads to increased cell death in C3H, DBA2 and FVB inbred mouse strains.
BACKGROUND
Drug abuse is common among adolescents and young adults. Although the consequences of intoxication are known, sequelae of drugs emerging on campuses and in clubs nationwide are not. We previously demonstrated that ketamine exposure results in lasting physiological abnormalities in mice. However, the extent to which these deficits reflect neuropathologic changes is not known.


METHODS
The current study examines neuropathologic changes following sub-anesthetic ketamine administration (5mg/kg i.p. x 5) to three inbred mouse strains. Stereologic quantification of silver stained nuclear and linear profiles as well as activated caspase-3 labeling was used to address: (1) whether or not ketamine increases excitotoxic and apoptotic cell death in hippocampal CA3 and (2) whether or not ketamine-induced cell death varies by genetic background.


RESULTS
Ketamine increased cell death in hippocampal CA3 of adult C3H, DBA2 and FVB mice. Neither silver staining nor activated caspase-3 labeling varied by strain, nor was there an interaction between ketamine-induced cell death and strain.


CONCLUSIONS
Ketamine exposure among young adults, even in limited amounts, may lead to irreversible changes in both brain function and structure. Loss of CA3 hippocampal cells may underlie persistent ERP changes previously shown in mice and possibly contribute to lasting cognitive deficits among ketamine abusers.
Majewski-Tiedeken
Chalon R
CR
Department of Psychiatry, Division of Neuropsychiatry, University of Pennsylvania, Philadelphia, PA 19104, United States.
Rabin
Cara R
CR
Siegel
Steven J
SJ
D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000473:pathology; D005071:Evoked Potentials / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D006624:Hippocampus / Q000473:pathology; D007150:Immunohistochemistry; D007649:Ketamine / Q000633:toxicity*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology; D020258:Neurotoxicity Syndromes / Q000235:genetics / Q000473:pathology*; D016622:Silver Staining; D013045:Species Specificity
D018691:Excitatory Amino Acid Antagonists; D007649:Ketamine; D053148:Caspase 3