The subthalamic nucleus keeps you high on emotion: behavioral consequences of its inactivation

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.

Subthalamic nucleus mediates the modulation on cocaine self-administration induced by ultrasonic 3 vocalizations playback in rats

“…It could be due to the fact that STN-lesioned rats were not able to decode the emotional properties of the USV. In fact STN-lesioned rats did not develop a preference or an aversion for the CPP/CPA compartment respectively paired with the 50- and 22-kHz USV, in agreement with their blunted emotional responses to both positive and negative stimuli previously reported (Pelloux et al 2014). The STN has long been considered a motor structure and is the target of the surgical treatment for patients with Parkinson’s disease using the High Frequency Stimulation (HFS), also called Deep Brain Stimulation (DBS) (Limousin et al 1995).…”

“…A total of 37 male Lister Hooded rats (Charles River Laboratories, Saint-Germain-sur-l’Arbresle, France) weighing ~290 g at their arrival were used. Animals were housed in pairs, maintained in animal facility and subjected to intra-jugular implantation of catheters and/or STN ibotenic excitotoxic lesions (rats underwent oral sucrose SA were only subjected to STN lesions) as previously described (Baunez et al 2005; Pelloux et al 2014; see Supporting Information). All the rats had free access to standard laboratory food pellets (Scientific Animal Food and Engineering, Augy, France) and water, except during the experimental sessions.…”

“…However, one can hypothesize that emotional and motivational processes may interact in the influence of proximal social factors on goal-directed behaviors. Therefore, the subthalamic nucleus (STN), a cerebral structure belonging to the basal ganglia, could represent an interesting candidate because it was previously shown to modulate affective responses to emotional stimuli (Pelloux et al 2014) and its inactivation reduces motivation for cocaine while increasing that for food only in a Progressive Ratio schedule of reinforcement but not in standard SA conditions (Baunez et al 2005; Rouaud et al 2010). In this study we thus aimed at evaluating the effects of 50- and 22- kHz USV playback on both cocaine and sucrose SA, and in both sham-control and STN-lesioned rats.…”

Mu-opioid receptor activation in the medial shell of nucleus accumbens promotes alcohol consumption, self-administration and cue-induced reinstatement

“…Importantly, opioid antagonists were given systemically in these studies and it is likely that opioid antagonists exert additional effects on palatability when administered outside of the NAc, for example, in the ventral pallidum (Smith and Berridge, 2007, 2005), where mu-opioid agonism enhances ‘liking’ for sucrose. Furthermore, the ingestive reactions measured in these alcohol studies include mouth movements, which in some taste reactivity studies are classified as neutral/consummatory and in some cases are not included in hedonic reaction scores (Castro and Berridge, 2014; Leeb et al, 1991; Pelloux et al, 2014; Richard and Berridge, 2011). It is also possible that if we had assessed palatability using a taste reactivity test, rather than lickometer analysis we would have found a different result.…”

La chirurgie au secours des addictions

“…Un modèle de perte de contrôle de la prise de drogue a été développé par Serge Ahmed et Georges Koob [40]. Dans ce modèle dans lequel un accès prolongé à la drogue est donné, nos résultats montrent que la stimulation profonde du noyau sousthalamique est efficace pour empêcher l'escalade de prise de drogue chez les animaux ( Figure 3C) (Pelloux, et al., en préparation) Il est toutefois intéressant de noter que l'inactivation du noyau sous-thalamique semble exercer son effet sur la motivation par un émoussement hédonique en réduisant les réponses affectives induites par du sucre ou de la quinine par exemple [41]. Ces résultats sont à rapprocher de certaines observations concernant les changements émotionnels observés chez les patients parkinsoniens soumis à une stimulation profonde du noyau sous-thalamique [42].…”