Pro-inflammatory Pharmacological Manipulations Associated with Depression: Effects of Peripheral Lipopolysaccharide Administration on Effort-related Decision Making in Operant Choice Procedures

Rationale. Several lines of evidence implicate pro-inflammatory cytokines (PICs) in some of the motivational symptoms of depression, such as fatigue, lassitude and anergia. For example, motivational symptoms are shown by people treated with the PIC interferon-α, and under conditions associated with elevated levels of PICs. Therefore, studies using manipulations that affect PICs may yield insights into the neural bases of psychomotor/motivational symptoms of depression. Objectives. The present experiments focused on the effects of the PIC inducer lipopolysaccharide (LPS) on effort-related choice behavior. Methods. Rats were tested on a concurrent fixed ratio 5 lever pressing/chow feeding choice procedure (FR5/choice), which assesses the tendency of rats to work for a preferred food (high carbohydrate pellets) in the presence of a freely available but less preferred option (laboratory chow). Previous work with this task has shown that interference with dopamine transmission decreases food-reinforced lever pressing but increases chow intake. Investigations assessed the ability of LPS to produce effort-related impairments on the FR5/choice task. In addition, studies examined whether LPS affected food intake, food preference, and core body temperature in the same dose range. Results. LPS (5.0 – 20.0 μg/kg IP) failed to shift choice behavior, producing significant decreases in lever pressing without increasing intake of the freely available chow. Furthermore, the suppression of lever pressing induced by LPS showed rapid tolerance (i.e., by the second injection). LPS (20.0 μg/kg IP) also significantly altered intake of the preferred high carbohydrate pellets in parallel free-feeding choice studies. This dose of LPS did not alter core body temperature. Conclusions. These results indicate that LPS may reduce the tendency to work for food, however it also causes a loss of appetite, which may be indicative of an overall “sickness” response, rather than a selective effect on effort-related choice