Enhanced food-related motivation after bilateral lesions of the subthalamic nucleus

Abstract

Although inactivation of the subthalamic nucleus (STN) has beneficial effects on motor symptoms of parkinsonism, little is known of possible actions on nonmotor symptoms of cognition or mood. Here, we used several forms of converging evidence to show that STN lesions can enhance behavioral motivation. Thus, bilateral fiber-sparing lesions of the STN in rats reduced the time required to eat a standard number of food reward pellets, without affecting food intake, and altered performance on a number of behavioral measures consistent with enhanced motivation for food. Thus, STN-lesioned rats showed greater levels of locomotor activity conditioned to food presentation, enhanced control over responding by food-related conditioned reinforcers, and a higher breaking point associated with elevated rate of lever press under a progressive ratio schedule of reinforcement. These results reveal a new functional role schedule for STN, possibly because of its involvement in ventral, as well as dorsal, striatal circuitry and are relevant to the therapeutic effects of STN stimulation in Parkinson's disease.

Fig. 1.

Photomicrographs of frontal sections stained with cresyl violet, at the level of the STN outlined by dashed lines, illustrating an STN in a sham (A) and in a lesioned (B) animal.

Fig. 2.

Effects of bilateral STN lesions on conditioned locomotor response for food over the various phases: habituation (A), conditioning (B), and extinction and prefeeding (C). Eachpoint represents the mean ± SEM number of cell-beam crosses during the first 30 min for the various daily sessions (abcissas). The activity is illustrated for sham control animals (open circles;n = 11) and for STN-lesioned rats (filled squares; n = 7).

Fig. 3.

Effects of post-training bilateral STN lesions on acquisition of responding with a conditioned reinforcer (CR). The number of lever presses on the lever producing the CS (CR lever) and on the control lever (NCR) are illustrated for sham (filled and open circles, respectively; n = 7) and lesioned (filled and open squares, respectively; n = 4) animals. Vertical bar, SEM.

Fig. 4.

Effects of bilateral STN lesions on performance in the PR task evaluated by the mean ± SEM last ratio reached during the session (i.e., breaking point) (A) and the rate of responding measured as the total number of lever presses per minute (±SEM) (B). Sham control animals (n= 8; open circles) and STN-lesioned animals (n = 7; filled squares) performance is illustrated over 10 sessions.