Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit.
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 (130 Hz, 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.
['Hachem-Delaunay|Sabira|S|', 'Fournier|Marie-Line|ML|', 'Cohen|Candie|C|', 'Bonneau|Nicolas|N|', 'Cador|Martine|M|', 'Baunez|Christelle|C|', 'Le Moine|Catherine|C|']
D000818:Animals D066272:Basolateral Nuclear Complex D003042:Cocaine D003342:Corpus Striatum D003598:Cytoskeletal Proteins D004558:Electric Stimulation D005917:Globus Pallidus D008297:Male D009419:Nerve Tissue Proteins D009474:Neurons D017397:Prefrontal Cortex D016760:Proto-Oncogene Proteins c-fos D051381:Rats D020318:Rats, Long-Evans D012201:Reward D020531:Subthalamic Nucleus
Addiction Arc c-Fos Striatum Basal ganglia Deep brain stimulation Nucleus accumbens Parkinson catFISH