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1.  DIFFERENTIAL REGULATION OF LOCOMOTOR ACTIVITY TO ACUTE AND CHRONIC COCAINE ADMINISTRATION BY ACID-SENSING ION CHANNEL 1A AND 2 IN ADULT MICE 
Neuroscience  2013;246:10.1016/j.neuroscience.2013.04.059.
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 ASIC1a−/− mice, cocaine induced a significantly less motor response at all doses (5, 10, 20, and 30 mg/kg), while in ASIC2−/− mice, cocaine (5–20 mg/kg) stimulated locomotor activity to an extent comparable to WT mice. Only at 30 mg/kg, the cocaine-stimulated motor activity was reduced in ASIC2−/− mice. In a chronic cocaine administration model (20 mg/kg, once daily for 5 days), a challenge injection of cocaine (10 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 ASIC1a−/− and ASIC2−/− mice. However, ASIC2−/− mice showed less sensitization to challenge cocaine when compared to WT and ASIC1a−/− 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.
doi:10.1016/j.neuroscience.2013.04.059
PMCID: PMC3855427  PMID: 23644053
acid-sensing ion channels; cocaine; stimulant; addiction; locomotor activity; behavioral sensitization
2.  Loss of surface N-methyl-d-aspartate receptor proteins in mouse cortical neurones during anaesthesia induced by chloral hydrate in vivo 
BJA: British Journal of Anaesthesia  2009;102(4):515-522.
Background
Anaesthetics may target ionotropic glutamate receptors in brain cells to produce their biological actions. Membrane-bound ionotropic glutamate receptors undergo dynamic trafficking between the surface membrane and intracellular organelles. Their subcellular distribution is subject to modulation by changing synaptic inputs and determines the efficacy and strength of excitatory synapses. It has not been explored whether anaesthesia has any impact on surface glutamate receptor expression. In this study, the effect of general anaesthesia on expression of N-methyl-d-aspartate (NMDA) receptors in the surface and intracellular pools of cortical neurones was investigated in vivo.
Methods
General anaesthesia was induced by intraperitoneal injection of chloral hydrate in adult male mice. Surface protein cross-linking assays were performed to detect changes in distribution of NMDA receptor subunits (NR1, NR2A, and NR2B) in the surface and intracellular compartments of cerebral cortical neurones.
Results
Chloral hydrate did not alter the total amounts of NR1, NR2A, and NR2B proteins in cortical neurones. However, the drug reduced NR1 proteins in the surface pool of these neurones, and induced a proportional increase in NR1 in the intracellular pool. Similar redistribution of NR2B subunits was observed between the two distinct pools. The changes in NR1 and NR2B were rapid and remained throughout the duration of anaesthesia. NR2A proteins were not altered in the surface or intracellular pool in response to chloral hydrate.
Conclusions
These data demonstrate that subcellular expression of NR1 and NR2B in cortical neurones is sensitive to anaesthesia. Chloral hydrate reduces surface-expressed NMDA receptors (specifically NR2B-containing NMDA receptors) in these neurones in vivo.
doi:10.1093/bja/aep009
PMCID: PMC2724878  PMID: 19224925
anaesthetics; cerebral cortex; glutamate receptor; NR1; NR2A; NR2B

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