The Influence of Subthalamic Nucleus Lesions on Sign-Tracking to Stimuli Paired with Food and Drug Rewards: Facilitation of Incentive Salience Attribution?

Abstract

It is well known that the subthalamic nucleus (STN) plays an important role in regulating motor function, but recent studies suggest the STN is also involved in regulating motivated behavior. For example, bilateral lesions of the STN increase motivation for both food and cocaine as assessed by 'breakpoint' on a progressive ratio schedule. However, the psychological mechanism(s) by which STN lesions increase motivation for rewards is unknown. We hypothesized that STN lesions might influence one specific component of motivation, the attribution of incentive value (incentive salience) to reward-related cues. We tested this hypothesis by quantifying the ability of a discrete cue that had been paired with the non-contingent delivery of either food or cocaine to elicit approach towards it (ie, to produce a 'sign-tracking' conditioned response, CR). STN lesions made prior to training increased asymptotic levels of sign-tracking behavior directed towards a cue paired with either food or cocaine. In addition, when STN lesions were made after animals had already undergone Pavlovian training, and animals were tested under extinction conditions, the STN lesion still facilitated a sign-tracking CR. Finally, reintroduction of the US (food) following extinction immediately restored robust sign-tracking behavior in animals with STN lesions. We speculate, therefore, that the STN is part of a neural system that moderates the amount of incentive salience attributed to reward-related stimuli. Activity in this neural system may help mitigate the development of compulsive behavioral disorders, such as addiction, which are characterized by pathological control over behavior by reward-associated cues.

Effects of prior amphetamine exposure on approach strategy in appetitive Pavlovian conditioning in rats

“…6 Locomotor activity in amphetamine-exposed and saline control rats in experiment 2 (in 5-min bins) during a 15-min pre-drug baseline period (bins 1-3) and 30 min (bins 4-9) after an amphetamine challenge injection (2 mg/kg, i.p.) subthalamic nucleus, which appear to similarly enhance incentive salience, increase sign-tracking behavior (Uslaner et al 2005(Uslaner et al , 2008. The present experiments, however, show that a regimen of amphetamine exposure which induced locomotor sensitization and which has been shown in other settings to enhance incentive salience attribution (Harmer and Phillips 1998;Mendez et al 2007) caused a decrease in sign-tracking (contact with the CS), while at the same time causing an increase in goal-tracking (approach to the site of reward delivery during the CS).…”

“…Support for this view comes from experiments in which lesions of the subthalamic nucleus, which have been shown to enhance motivation for both food and drugs of abuse, enhance sign-tracking to visual cues paired with these rewards (Baunez et al 2002;Uslaner et al 2005Uslaner et al , 2008. In the present experiments, however, amphetamine exposure, which has motivation-enhancing effects similar to those of subthalamic nucleus lesions (Ferrario and Robinson 2007;Mendez et al 2007;Nordquist et al 2007), had the opposite effect on sign-tracking.…”

Surgical Strategies for Parkinson’s Disease Based on Animal Model Data: GPi and STN Inactivation on Various Aspects of Behavior (Motor, Cognitive and Motivational Processes)

“…When assessing motivation by measures of reactivity to stimuli predicting food, we found that STN lesions increase responses to these stimuli [61]. This result was further confirmed by Uslaner and colleagues [64]. We also showed that STN lesions increase willingness to work on a lever to obtain food pellets and increase the score of preference for an environment previously associated with food [62].…”

Subthalamic nucleus stimulation affects incentive salience attribution in Parkinson's disease

“…[16][17][18] This dopamine-mediated behavior also seems to be modulated by the control of the STN, as both the subthalamotomy and the STN DBS increased motivation for food in experimental animals. [19][20][21][22][23][24] The role of STN in emotional and motivational processing was also demonstrated in neurophysiological studies in monkeys and in PD patients. …”