Abstract

The subthalamic nucleus (STN) belongs to the basal ganglia and is the current target for the surgical treatment of neurological and psychiatric disorders such as Parkinson’s Disease (PD) and obsessive compulsive disorders (OCD), but also a proposed site for the treatment of addiction. It is therefore very important to understand its functions in order to anticipate and prevent possible side-effects in the patients. Although the involvement of the STN is well documented in motor, cognitive and motivational processes, less is known regarding emotional processes. Here we have investigated the direct consequences of STN inactivation by excitotoxic lesions on emotional processing and reinforcement in the rat. We have used various behavioral procedures to assess affect for neutral, positive and negative reinforcers in STN lesioned rats. STN lesions reduced affective responses for positive (sweet solutions) and negative (electric foot shock, Lithium Chloride-induced sickness) reinforcers while they had no effect on responses for a more neutral reinforcer (novelty induced place preference (NIPP)). Furthermore, when given the choice between saccharine, a sweet but non caloric solution, and glucose, a more bland but caloric solution, in contrast to sham animals that preferred saccharine, STN lesioned animals preferred glucose over saccharine. Taken altogether these results reveal that STN plays a critical role in emotional processing. These results, in line with some clinical observations in PD patients subjected to STN surgery, suggest possible emotional side-effects of treatments targeting the STN. They also suggest that the increased motivation for sucrose previously reported cannot be due to increased pleasure, but could be responsible for the decreased motivation for cocaine reported after STN inactivation.

Highlights

  • The subthalamic nucleus (STN) belongs to the basal ganglia

  • In the present study, we have shown that STN lesions have little effect on neutral affective response as assessed in the NOVELTY INDUCED PLACE PREFERENCE (NIPP)

  • Pleasant responses to sweet solutions were diminished by the STN inactivation

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Summary

Introduction

The subthalamic nucleus (STN) belongs to the basal ganglia. Its hyperactivity in Parkinson’s Disease (PD) leads to targeting it as a surgical treatment using High Frequency Stimulation (HFS) in PD patients (for review Benabid et al, 2006). Emotional disturbances have been reported such as decreases in physiological arousal and in the recognition of emotional expressions and subjective feelings (Péron et al, 2013) Whether or not these effects are directly due to the STN manipulation or due to modifications in the dopaminergic supply to these patients remains a matter a debate. The STN manipulation does not necessarily imply that STN itself should be involved in emotional processes, since HFS does reduce electrophysiological activity of the targeted structure, and induces orthodromic and antidromic stimulation (McCracken and Grace, 2007). It is important to better understand the contribution of STN itself in emotional processing in an intact brain, especially since STN HFS is currently applied for psychiatric disorders such as OCD (Mallet et al, 2008), and proposed for treatment of addiction (Pelloux and Baunez, 2013)

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