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bioRxiv · 10.64898/2026.09.29.755395

The basolateral amygdala dopamine system shapes dynamic drug seeking states

Brickner, M. A.·Szot, W. E.·Prohofsky, J. M.·Wolff, A. R.·Thomas, M. J.·Saunders, B. T.
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Abstract

Drug-associated sensory cues and contexts exert powerful influence over drug seeking motivation, but in vivo brain mechanisms governing this process remain unclear. Here, we recorded and manipulated dopamine signaling and dopamine receptor D1+ neuronal activity in the basolateral amygdala (BLA) to investigate their contributions to dynamic sensory-guided cocaine seeking in rats. First, we show that cocaine exposure sensitizes dopamine transmission from ventral tegmental area dopamine neurons projecting to the BLA. We then employed an intermittent access cocaine self-administration paradigm that prompted robust binge-like cocaine seeking that was heavily guided by shifts in the sensory environment. Cued transitions to drug available states evoked large and sustained BLA dopamine signals and transient neuronal responses from BLA D1+ neurons. BLA dopamine signals and D1-neuron activity came to preferentially encode these drug availability states, which hierarchically modulated neural activity during drug seeking actions and predicted different aspects of behavior. Finally, we found that optogenetically enhancing BLA D1-neuron activity at drug availability state transitions potentiated cocaine binging. Our findings provide new insight into the neural control of addiction-related behavior, identifying the dopaminergic amygdala as a key interface between the environment and decisions to engage in vigorous drug use.

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Brickner, M. A., Szot, W. E., Prohofsky, J. M., Wolff, A. R., Thomas, M. J., Saunders, B. T.. 2026-10-08. The basolateral amygdala dopamine system shapes dynamic drug seeking states. https://doi.org/10.64898/2026.09.29.755395

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