Transcript Slide 1

Regulation of Locomotor Activity to Amphetamine Injection by Acid-sensing Ion Channels 1a and 2 in Adult Mice
Comron Jon Hassanzadeh, Xiangping Chu
UMKC School of Medicine
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Fig. 1. Effects of acute and chronic AMPH injection on total distance in WT, ASIC1 and
ASIC2 mice.
* < 0.05 as compared to WT mice in each day. # < 0.05 as compared to day 1 WT mice. & <
0.05 as compared to day 1 WT mice. KO, knock-out,
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ASIC1 KO (n=15)
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Fig. 2 Effects of acute and chronic AMPH injection on horizontal activity in WT, ASIC1
and ASIC2 KO mice
Chronic AMPH Treatment
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Acute AMPH Treatment
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Total distance traveled
in post 90 min (m)
Total distance traveled
in post 90 min (m)
•Adult male and female C57BL/6J (WT),
ASIC1a-/- and ASIC2-/- mice received a single
intraperitoneal injection (IP) of AMPH at
3mg/kg, and their locomotor activity (LM)
was recorded for 90 minutes. Repeated for 5
days.
•After a two-week withdrawal period, the mice
underwent an accommodation period for 60
minutes in individual test chambers.
•A challenge IP injection of 1.5mg/kg AMPH
was administered, and LM activity at this
dose was measured for 90 minutes.
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Acute AMPH Treatment
Horizontal activity in post 90 min
(beam breaks per 5 min)
•Acute AMPH injection induced a typical dosedependent increase in LM activities (total
distance (TD) and horizontal activity (HA)) in
WT, ASIC1, and ASIC2 KO (knock-out) mice.
•However, increase in LM activities were
attenuated in ASIC1 KO mice as compared to
WT.
•ASIC2 showed decreased LM activity on days
two and three as compared to WT
•Chronic sensitization showed no difference
when comparing WT to ASIC1 or ASIC2
•Acid-sensing ion channels (ASICs) are protongated, voltage-independent channels that
participate in neuronal transmission in the
CNS.1
•There is evidence of alterations in subcellular
expression of ASICs, particularly ASIC1a, in
the rat forebrain following chronic
amphetamine (AMPH) administration.
•This may constitute a key synaptic adaptation in
reward circuits critical for psychomotor
plasticity. 2
Horizontal activity in post 90 min
(beam breaks per 5 min)
RESULTS
INTRODUCTION
METHODS
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CONCLUSION
•Acute and chronic administration of AMPH
appeared to elicit different phenotypic
responses in the adult mice.
•ASIC1a likely plays a role in acute drug
administration given the dampened
response seen in the KO mice
•ASIC2’s role in acute or chronic drug
administration remains difficult to determine
•ASIC1a may prove to be a pharmacotherapy
target for dampening acute drug responses
with future studies.
REFERENCES/ACKNOWLEDGEMENTS
1. Chu and Xiong. Current Drug Targets. (2012) 13: 263-271.
2. Suman et al. Neurosci Res. (2010) 68(1): 1-8.
3. Jiang et al. Neurosci. (2013) 246: 170-178
•Special thanks to Dr. Chu, Qian, UMKC, and the Sarah Morrison
Award for their generous contributions