title: Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit.
abstract: 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.
authors.affiliation: Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France; CNRS, INCIA, UMR 5287, Bordeaux F-33000, France.
authors.forename: Sabira
authors.initials: S
authors.lastname: Hachem-Delaunay
authors.affiliation: Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France; CNRS, INCIA, UMR 5287, Bordeaux F-33000, France.
authors.forename: Marie-Line
authors.initials: ML
authors.lastname: Fournier
authors.affiliation: CNRS, INT, UMR 7289, Marseille F-13385, France; Aix Marseille Université, INT, UMR 7289, Marseille F-13385, France.
authors.forename: Candie
authors.initials: C
authors.lastname: Cohen
authors.affiliation: Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France; CNRS, INCIA, UMR 5287, Bordeaux F-33000, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Bonneau
authors.affiliation: Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France; CNRS, INCIA, UMR 5287, Bordeaux F-33000, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Cador
authors.affiliation: CNRS, INT, UMR 7289, Marseille F-13385, France; Aix Marseille Université, INT, UMR 7289, Marseille F-13385, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Baunez
authors.affiliation: Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France; CNRS, INCIA, UMR 5287, Bordeaux F-33000, France. Electronic address: catherine.le-moine@u-bordeaux.fr.
authors.forename: Catherine
authors.initials: C
authors.lastname: Le Moine
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000378:metabolism; D003042:Cocaine / Q000008:administration & dosage*; D003342:Corpus Striatum / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004558:Electric Stimulation; D005917:Globus Pallidus / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D020531:Subthalamic Nucleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; D016760:Proto-Oncogene Proteins c-fos; C092069:activity regulated cytoskeletal-associated protein; D003042:Cocaine
keywords: Addiction; Arc; Basal ganglia; Deep brain stimulation; Nucleus accumbens; Parkinson; Striatum; c-Fos; catFISH