Subthalamic nucleus high-frequency stimulation modulates neuronal reactivity to cocaine within the reward circuit
Neurobiology of Disease. 2015-08-01; 80: 54-62
DOI: 10.1016/j.nbd.2015.05.007
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Hachem-Delaunay S(1), Fournier ML(1), Cohen C(2), Bonneau N(1), Cador M(1),Baunez C(2), Le Moine C(3).
Author information:
(1)Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France; CNRS, INCIA, UMR 5287, Bordeaux F-33000, France.
(2)CNRS, INT, UMR 7289, Marseille F-13385, France; Aix Marseille Université, INT, UMR 7289, Marseille F-13385, France.
(3)Université Bordeaux, INCIA, UMR 5287, Bordeaux F-33000, France; CNRS, INCIA, UMR 5287, Bordeaux F-33000, France. Electronic address: .
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.
Copyright © 2015 Elsevier Inc. All rights reserved.
DOI: 10.1016/j.nbd.2015.05.007
PMID: 25982833 [Indexed for MEDLINE]