Source Paper
Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex
Bita Moghaddam, Barbara Adams, Anita Verma, Darron Daly
Journal of Neuroscience • 1997
Spatial Delayed Alternation Task
Objective: Assess impairment of cognitive function in rodents following ketamine treatment using a prefrontal cortex-sensitive spatial delayed alternation task
Protocol Steps
Dose-response study with microdialysis
Conduct microdialysis in conscious rats to measure glutamate outflow in the prefrontal cortex following ketamine administration
Note: Multiple doses tested: 10, 20, 30, 50, and 200 mg/kg
View evidence from paper
“A thorough dose-response study using microdialysis in conscious rats indicated that low doses of ketamine (10, 20, and 30 mg/kg) increase glutamate outflow in the PFC”
Measure dopamine release
Measure dopamine release in the prefrontal cortex following ketamine administration at 30 mg/kg dose
Note: 30 mg/kg dose selected based on glutamate findings
View evidence from paper
“Ketamine, at 30 mg/kg, also increased the release of dopamine in the PFC”
Test CNQX blockade of dopamine release
Apply CNQX (AMPA/kainate receptor antagonist) intra-PFC to determine if it blocks ketamine-induced dopamine release
Note: Intra-PFC application of antagonist
View evidence from paper
“This increase was blocked by intra-PFC application of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione CNQX”
Spatial delayed alternation task with LY293558 pretreatment
Administer LY293558 systemically as pretreatment prior to ketamine administration, then assess performance on spatial delayed alternation task
Note: Systemic pretreatment with AMPA/kainate receptor antagonist
View evidence from paper
“ketamine-induced activation of dopamine release and impairment of spatial delayed alternation in the rodent, a PFC-sensitive cognitive task, was ameliorated by systemic pretreatment with AMPA/kainate receptor antagonist LY293558”