Single Dose of Amphetamine Induces Delayed Subregional Attenuation of Cholinergic Interneuron Activity in the Striatum

Abstract Psychostimulants such as amphetamine (AMPH) target dopamine (DA) neuron synapses to engender drug-induced plasticity. While DA neurons modulate the activity of striatal (Str) cholinergic interneurons (ChIs) with regional heterogeneity, how AMPH affects ChI has not been elucidated. Here, we applied quantitative fluorescence imaging approaches map dose-dependent effects a single dose on at 2.5 and 24 h after injection across mouse Str using activity-dependent marker phosphorylated ribosomal protein S6 (p-rpS6 240/244 ). did affect distribution or morphology ChIs in any subregion. either had no effect h, was dependently reduced specifically ventral Str/nucleus accumbens (NAc), critical site psychostimulant action. spontaneous firing ChIs. Altogether this work demonstrates that delayed regionally heterogeneous activity, which most likely involves extra-Str synaptic input.