Source Paper
Prepulse Inhibition Deficits and Perseverative Motor Patterns in Dopamine Transporter Knock-Out Mice: Differential Effects of D1 and D2 Receptor Antagonists
Rebecca J. Ralph, Martin P. Paulus, Fabio Fumagalli, Marc G. Caron, Mark A. Geyer
Journal of Neuroscience • 2001
Prepulse Inhibition of Startle Response
Objective: Measurement of sensorimotor gating by assessing prepulse inhibition of the acoustic startle response in dopamine transporter knock-out mice, and evaluation of D1 and D2 receptor antagonist effects on PPI and motor behavior
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Equipment2
Materials2
Software1
Not specified • Not specified
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Protocol Steps
Baseline behavioral assessment
Assess baseline prepulse inhibition of startle response, locomotor patterns, and activity levels in DAT (-/-) mice and DAT (+/+) control mice
Note: DAT (-/-) mice exhibited deficient sensorimotor gating, nonfocal perseverative locomotion patterns, and hyperactivity compared to controls
View evidence from paper
“At baseline, DAT (-/-) mice exhibited deficient sensorimotor gating as measured by prepulse inhibition (PPI) of the startle response, exhibited nonfocal perseverative patterns of locomotion, and were hyperactive in a novel environment”
Pretreatment with D2 receptor antagonist
Administer raclopride as a pretreatment to DAT (-/-) mice
Note: Raclopride is a preferential dopamine D2 receptor antagonist
View evidence from paper
“Pretreatment with raclopride significantly increased PPI in the DAT (-/-) mice”
Measure PPI following D2 antagonist treatment
Assess prepulse inhibition of startle response following raclopride pretreatment
Note: Raclopride significantly increased PPI in DAT (-/-) mice
View evidence from paper
“Pretreatment with raclopride significantly increased PPI in the DAT (-/-) mice”
Pretreatment with D1 receptor antagonist
Administer SCH23390 as a pretreatment to DAT (-/-) mice
Note: SCH23390 is a D1 receptor antagonist
View evidence from paper
“challenging them with the preferential dopamine D2 receptor antagonist raclopride and D1 receptor antagonist SCH23390”
Measure PPI following D1 antagonist treatment
Assess prepulse inhibition of startle response following SCH23390 pretreatment
Note: SCH23390 had no significant effect on PPI in DAT (-/-) mice
View evidence from paper
“SCH23390 had no significant effect”
Assess motor behavior patterns following D2 antagonist
Evaluate locomotor patterns and motor behavior following raclopride treatment
Note: D2 receptor blockade did not affect the predominantly straight perseverative patterns of motor behavior
View evidence from paper
“Blockade of D2 receptors did not affect the predominantly straight patterns of motor behavior produced by the DAT (-/-) mice”
Assess motor behavior patterns following D1 antagonist
Evaluate locomotor patterns and motor behavior following SCH23390 treatment
Note: D1 receptor antagonism significantly attenuated perseverative patterns, producing more meandering behavior similar to wild-type controls
View evidence from paper
“antagonism of D1 receptors significantly attenuated the perseverative patterns, producing more of a meandering behavior seen in the DAT (+/+) control mice”
Measure activity levels following antagonist treatments
Assess hyperactivity levels in DAT (-/-) mice following both D1 and D2 receptor antagonist treatments
Note: Both D1 and D2 receptor antagonists decreased hyperactivity in DAT (-/-) mice
View evidence from paper
“Both D1 and D2 receptor antagonists decreased the hyperactivity seen in the DAT (-/-) mice”