Abstract
Acid-sensing ion channels (ASICs) are densely expressed in broad areas of mammalian brains and actively modulate synaptic transmission and a variety of neuronal activities. To explore whether ASICs are linked to addictive properties of drugs of abuse, we investigated the effect of the psychostimulant amphetamine on subcellular ASIC expression in the rat forebrain in vivo. Repeated administration of amphetamine (once daily for 7 days, 1.25 mg/kg for days 1/7, 4 mg/kg for days 2-6) induced typical behavioral sensitization. At a 14-day withdrawal period, ASIC1 protein levels were increased in the defined surface and intracellular compartments in the striatum (both caudate putamen and nucleus accumbens) in amphetamine-treated rats relative to saline-treated rats as detected by a surface protein cross-linking assay. ASIC2 proteins, however, remained stable in the striatum. In the medial prefrontal cortex, repeated amphetamine administration had no effect on ASIC1 expression in either the surface or the intracellular pool. However, amphetamine selectively reduced the surface expression of ASIC2 in this region. These data identify ASICs as a sensitive target to repeated stimulant exposure. The region- and compartment-specific regulation of ASIC1 and ASIC2 expression may constitute a key synaptic adaptation in reward circuits critical for psychomotor plasticity.