Comron Jon Hassanzadeh, Xiangping Chu UMKC School of Medicine 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 INTRODUCTION Acid-sensing ion channels (ASICs) are proton- gated, 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 RESULTS Acute AMPH injection induced a typical dose- dependent 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 Select from logos at the bottom of the page to place with UMKC School of Medicine in upper right corner. Delete unused logos. May add other institutions, if applicable. Fig. 2 Effects of acute and chronic AMPH injection on horizontal activity in WT, ASIC1 and ASIC2 KO mice 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. METHODS 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. 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 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, Special thanks to Dr. Chu, Qian, UMKC, and the Sarah Morrison Award for their generous contributions