Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit

Neurobiology of Disease

Christelle Baunez¹  Marie-Line Fournier²  Nicolas Bonneau²  Martine Cador³  Sabira Hachem-Delaunay⁴  Catherine Le Moine⁴  Candie Cohen⁴ 

[1] Aix Marseille Université, INT, UMR 7289, Marseille F-13385, France;CNRS, INCIA, UMR 5287, Bordeaux F-33000, France;CNRS, INT, UMR 7289, Marseille F-13385, France;Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France;

关键词: Addiction;    Parkinson;    Basal ganglia;    Arc;    c-Fos;    catFISH;   

DOI  :  

来源: DOAJ

【 摘 要 】

The subthalamic nucleus (STN) is a critical component of a complex network controlling motor, associative and limbic functions. High-frequency stimulation (HFS) of the STN is an effective therapy for motor symptoms in Parkinsonian patients and can also reduce their treatment-induced addictive behaviors. Preclinical studies have shown that STN HFS decreases motivation for cocaine while increasing that for food, highlighting its influence on rewarding and motivational circuits. However, the cellular substrates of these effects remain unknown. Our objectives were to characterize the cellular consequences of STN HFS with a special focus on limbic structures and to elucidate how STN HFS may interfere with acute cocaine effects in these brain areas. Male Long–Evans rats were subjected to STN HFS (130Hz, 60 μs, 50–150 μA) for 30 min before an acute cocaine injection (15 mg/kg) and sacrificed 10 min following the injection. Neuronal reactivity was analyzed through the expression of two immediate early genes (Arc and c-Fos) to decipher cellular responses to STN HFS and cocaine. STN HFS only activated c-Fos in the globus pallidus and the basolateral amygdala, highlighting a possible role on emotional processes via the amygdala, with a limited effect by itself in other structures. Interestingly, and despite some differential effects on Arc and c-Fos expression, STN HFS diminished the c-Fos response induced by acute cocaine in the striatum. By preventing the cellular effect of cocaine in the striatum, STN HFS might thus decrease the reinforcing properties of the drug, which is in line with the inhibitory effect of STN HFS on the rewarding and reinforcing properties of cocaine

【 授权许可】

Unknown