Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking

Mickaël Degoulet , Alix Tiran-Cappello , Christelle Baunez (1) , Yann Pelloux

1 INT - Institut de Neurosciences de la Timone

Cocaine seeking despite a foot-shock contingency is used to model compulsive drug seeking, a core component of drug addiction, in rodents. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is efficient on other addiction criteria models and we show here that 30-Hz STN stimulation reduces pathological cocaine seeking in compulsive-like rats. This confirms STN DBS as a potential strategy to treat addiction. We also observed that only ‘compulsive-like’ rats displayed a progressive increase in STN low frequency oscillations, especially in the alpha/theta band (6-13 Hz), during cocaine escalation. Conversely, applying 8-Hz STN DBS to mimic alpha/theta oscillations in ‘non-compulsive’ animals changed them into ‘compulsive’ ones. We have thus identified a predictive neuronal biomarker of compulsivity. Since one critical challenge in addiction research is to identify vulnerable individuals before they transition to harmful drug consumption pattern, our results could lead to new diagnostic tools and prevention strategies.

Cocaine seeking despite a foot-shock contingency is used to model compulsive drug seeking, a core component of drug addiction, in rodents. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is efficient on other addiction criteria models and we show here that 30-Hz STN stimulation reduces pathological cocaine seeking in compulsive-like rats. This confirms STN DBS as a potential strategy to treat addiction. We also observed that only ‘compulsive-like’ rats displayed a progressive increase in STN low frequency oscillations, especially in the alpha/theta band (6-13 Hz), during cocaine escalation. Conversely, applying 8-Hz STN DBS to mimic alpha/theta oscillations in ‘non-compulsive’ animals changed them into ‘compulsive’ ones. We have thus identified a predictive neuronal biomarker of compulsivity. Since one critical challenge in addiction research is to identify vulnerable individuals before they transition to harmful drug consumption pattern, our results could lead to new diagnostic tools and prevention strategies.

Domaines: Neurosciences; Neurobiologie; Psychologie et comportements; Pharmacologie

Mickaël Degoulet, Alix Tiran-Cappello, Christelle Baunez, Yann Pelloux. Low frequency oscillatory activity of the subthalamic nucleus is a predictive biomarker of compulsive-like cocaine seeking. 2019. ⟨hal-02990841⟩