Analysis Tools
behavior/neurological
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• mice show increased susceptibility to amphetamine-induced hyperactivity
• after habituation to a novel open field environment, administration of amphetamine causes over 2.5-fold greater hyperactivity in mutants than in wild-type mice over a 30 minute period
• amphetamine shows a lower threshold for hyperactivity in mutants than in wild-type mice
• mutants show a 19 and 59% increase in hyperactivity after 2 and 3 weekly treatments with amphetamine compared to wild-type mice that do not show sensitization to this low-dose repeated administration
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• while both wild-type and mutant mice show failure to escape foot shocks after conditioning with random, mild inescapable foot shocks, when the level of aversive stimuli is reduced to a level that does not cause failure to escape in wild-type mice, 91% of mutants fail to escape foot shocks, indicating increased susceptibility to stress-induced depressive-like behavior
• mutants exhibit a longer escape latency compared to wild-type mice and this behavior persists throughout 30 trials unlike in wild-type mice that show longer escape latency only in the first five trials
• in a fear conditioning paradigm, freezing time is 28% higher than in wild-type upon exposure to the contextual test 24 hours later
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• upon exposure to a novel context (pretone cue test), mutants initially show 59% less freezing than wild-type mice
• however, when exposed to a tone paired with the new context, mutants exhibit normal freezing times, indicating intact amygdalar function
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• mutants exhibit heightened response to novel environment, showing an initial increase in hyperactivity compared to wild-type mice when placed in an open field
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• in the forced swim test and tail suspension test, mutants spend 29% and 27% more time, respectively, immobile than wild-type mice, indicating increased susceptibility to stress-induced depressive-like behaviors
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• mutants show mild-anxious behavior in the elevated plus maze, spending 44% less time in the open arms of the maze and longer time in the closed arms of the maze than wild-type mice
• without previous conditioning by inescapable foot shocks, 32% of mutants fail to escape foot shocks compared to none in wild-type mice
• administration of lipopolysaccharide (LPS) 24 hours after aversive stress (foot shocks) results in an additional increase in immobility time
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• mutants show only slight thigmotaxis in the open field during the first 5 minutes of testing but not overall throughout 15 minutes, indicating that a new environment may trigger anxiety
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• mice exhibit hyperactivity in novel, but not familiar, environment; when mutants are placed in an open field, they initially show modest hyperactivity but are able to habituate to normal levels with repeat testing in the same open field
• chronic lithium administration partially reduces amphetamine-induced hyperactivity to the level equivalent to wild-type mice receiving amphetamine treatment
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homeostasis/metabolism
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• while baseline levels of corticosterone are similar to wild-type mice, immediately following an inescapable foot shock session, mutants exhibit increased serum corticosterone levels compared to wild-type
• lithium pretreatment results in serum corticosterone levels similar to wild-type mice following an inescapable foot shock session
• following escapable foot shock session, serum corticosterone levels are also increased but not as much as after inescapable foot shock
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• administration of lipopolysaccharide (LPS) 24 hours after aversive stress (foot shocks) results in an increase in IL-6 serum levels compared to wild-type
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nervous system
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• NMDA receptor-dependent LTD induced by low frequency stimulation is converted to a slow onset LTP-like response in the hippocampus
• however, baseline synaptic transmission and paired pulse ratio are normal
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immune system
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• administration of lipopolysaccharide (LPS) 24 hours after aversive stress (foot shocks) results in an increase in IL-6 serum levels compared to wild-type
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