Drug Response Testing in DAT Knockout Mice
Objective: Evaluation of wake-promoting drug responsiveness (modafinil, methamphetamine, GBR12909, and caffeine) in DAT knockout mice to determine the role of dopamine transporters in stimulant-induced wakefulness
Protocol Steps
Baseline sleep-wake recording
Establish baseline polygraphic recordings in DAT knockout mice and wild-type controls
Note: Baseline measurements needed to assess changes in sleep-wake patterns
View evidence from paper
“polygraphic recordings and caudate microdialysate dopamine measurements”
Drug administration - Modafinil
Administer modafinil to DAT knockout mice and assess wake-promoting response via polygraphic recording
Note: DAT knockout mice showed no responsiveness to modafinil wake-promoting effects
View evidence from paper
“DAT knock-out mice were also unresponsive to the normally robust wake-promoting action of modafinil”
Drug administration - Methamphetamine
Administer methamphetamine to DAT knockout mice and assess wake-promoting response
Note: DAT knockout mice showed no responsiveness to methamphetamine
View evidence from paper
“unresponsive to the normally robust wake-promoting action of modafinil, methamphetamine”
Drug administration - GBR12909
Administer selective DAT blocker GBR12909 to DAT knockout mice and assess wake-promoting response
Note: DAT knockout mice showed no responsiveness to GBR12909
View evidence from paper
“unresponsive to the normally robust wake-promoting action of modafinil, methamphetamine, and the selective DAT blocker GBR12909”
Drug administration - Caffeine
Administer caffeine to DAT knockout mice and assess wake-promoting response
Note: DAT knockout mice showed hypersensitivity to caffeine wake-promoting effects
View evidence from paper
“were hypersensitive to the wake-promoting effects of caffeine”
Dopamine measurement
Measure extracellular dopamine in caudate region during drug administration
Note: Microdialysate dopamine measurements correlate with behavioral responses
View evidence from paper
“caudate microdialysate dopamine measurements in narcoleptic dogs revealed that the wake-promoting antinarcoleptic compounds modafinil and amphetamine increase extracellular dopamine”