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Assessment of Dopaminergic Homeostasis in Mice by Use of High-performance Liquid Chromatography Analysis and Synaptosomal Dopamine Uptake
Published on: September 21, 2017
Impaired cliff avoidance reaction in dopamine transporter knockout mice
Motoyasu Yamashita1, Yasufumi Sakakibara, F Scott Hall
1Department of Biological Psychiatry, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Psychopharmacology
|February 12, 2013
Summary
Dopamine transporter knockout mice show significant impulsivity and attention deficits, similar to attention-deficit/hyperactivity disorder (ADHD). Treatments targeting monoamine transporters improved impulsive behaviors in these mice.
Area of Science:
- Neuroscience
- Behavioral Science
Background:
- Impulsivity is a core symptom of attention-deficit/hyperactivity disorder (ADHD).
- The cliff avoidance reaction (CAR) is a rodent model for impulsive behavior.
- Dopamine transporter knockout (DAT-KO) mice exhibit ADHD-like traits.
Purpose of the Study:
- To assess impulsivity in DAT-KO mice using the CAR paradigm.
- To compare attentional deficits in DAT-KO mice via prepulse inhibition (PPI).
- To investigate the effects of methylphenidate and nisoxetine on CAR impairments.
Main Methods:
- DAT-KO mice and wild-type (WT) littermates were used.
- Behavioral assessments included the cliff avoidance reaction (CAR) and prepulse inhibition (PPI).
- Pharmacological treatments involved methylphenidate and nisoxetine.
Main Results:
- DAT-KO mice demonstrated significant CAR impairments compared to WT mice.
- DAT-KO mice exhibited deficits in PPI, indicating impaired sensorimotor gating.
- A correlation was observed between CAR impairment severity and PPI deficits in DAT-KO mice.
- Methylphenidate and nisoxetine treatments reduced CAR impairments in DAT-KO mice.
Conclusions:
- DAT-KO mice display impulsive behavior in the CAR test, correlating with sensorimotor gating deficits.
- Pharmacological interventions targeting monoamine transporters, particularly norepinephrine transporter (NET) in the prefrontal cortex (PFC), may alleviate impulsivity.
