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Updated: Dec 11, 2025

Using Optogenetics to Reverse Neuroplasticity and Inhibit Cocaine Seeking in Rats
Published on: October 5, 2021
Amphetamine reduces reward encoding and stabilizes neural dynamics in rat anterior cingulate cortex
Saeedeh Hashemnia1, David R Euston1, Aaron J Gruber1
1Canadian Center for Behavioral Neuroscience, Department of Neuroscience, University of Lethbridge, Lethbridge, Canada.
Abstract:
Psychostimulants such as d-amphetamine (AMPH) often have behavioral effects that appear paradoxical within the framework of optimal choice theory. AMPH typically increases task engagement and the effort animals exert for reward, despite decreasing reward valuation. We investigated neural correlates of this phenomenon in the anterior cingulate cortex (ACC), a brain structure implicated in signaling cost-benefit utility. AMPH decreased signaling of reward, but not effort, in the ACC of freely-moving rats. Ensembles of simultaneously recorded neurons generated task-specific trajectories of neural activity encoding past, present, and future events. Low-dose AMPH contracted these trajectories and reduced their variance, whereas high-dose AMPH expanded both. We propose that under low-dose AMPH, increased network stability balances moderately increased excitability, which promotes accelerated unfolding of a neural 'script' for task execution, despite reduced reward valuation. Noise from excessive excitability at high doses overcomes stability enhancement to drive frequent deviation from the script, impairing task execution.
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