کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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6274579 | 1614830 | 2013 | 9 صفحه PDF | دانلود رایگان |
- ASIC1aâ/â mice showed highest frequency of jumps compared to WT and ASIC2â/â mice.
- ASIC1aâ/â mice displayed reduced locomotor responses to acute cocaine injection.
- ASIC2â/â mice showed locomotor activity comparable to WT mice to acute cocaine.
- ASIC2â/â mice showed less sensitization to challenge cocaine.
Acid-sensing ion channels (ASICs) are densely expressed in the brain with ASIC1a and ASIC2 channels being the predominant subtypes. These channels are enriched at synaptic sites and are central for the regulation of normal synaptic transmission. Moreover, increasing evidence links ASICs to the pathogenesis of various neurological and neuropsychiatric disorders. In this study, we explore the putative role of ASIC1a and ASIC2 in the regulation of behavioral sensitivity to the psychostimulant cocaine by utilizing ASIC1a or ASIC2 knockout mice. Acute cocaine injection induced a typical dose-dependent increase in locomotor activities in wild-type (WT) mice. However, in ASIC1a and ASIC2 mutant mice, different motor responses to cocaine were observed. In ASIC1aâ/â mice, cocaine induced a significantly less motor response at all doses (5, 10, 20, and 30Â mg/kg), while in ASIC2â/â mice, cocaine (5-20Â mg/kg) stimulated locomotor activity to an extent comparable to WT mice. Only at 30Â mg/kg, the cocaine-stimulated motor activity was reduced in ASIC2â/â mice. In a chronic cocaine administration model (20Â mg/kg, once daily for 5Â days), a challenge injection of cocaine (10Â mg/kg, after 2-week withdrawal) caused an evident behavioral sensitization in the cocaine-pretreated WT mice. This behavioral sensitization to challenge cocaine was also displayed in ASIC1aâ/â and ASIC2â/â mice. However, ASIC2â/â mice showed less sensitization to challenge cocaine when compared to WT and ASIC1aâ/â mice. Our results demonstrate the important role of ASIC1a and ASIC2 channels in the modulation of behavioral sensitivity to cocaine. The two synapse-enriched ASIC subtypes are believed to play distinguishable roles in the regulation of behavioral responses to acute and chronic cocaine administration.
Journal: Neuroscience - Volume 246, 29 August 2013, Pages 170-178