Lipopolysaccharide, central in vivo biogenic amine variations, and anhedonia

SYSTEMIC administration of lipopolysaccharide (LPS), a non-specific activat or of proinflammatory cytokine release from macrophages, provokes sickness characterized by anorexia, soporific effects, and disturbances of locomotor activity and exploration. In addition, endotoxin treatment may provoke an anhedonic response. Assessment of anhedonia in appetitive paradigms, howeve r, is compromised by the anorexia provoked resent investigation assessed by the treatment. The LPS on rewarding lateral the anhedonic effects hypothal amic brain stimulation. Using a simultaneous discrimination, current titrat ion procedure in the assessment of intracranial self-stimulation (ICSS), it was found that acute systemic administration of LPS (50 mu g, 100 mu g or 200 mu g) reduced ICSS during the ascending sequence of current presentatio ns, but had little effect on responding to a series of descending currents. In a parallel experiment, peripheral administration of LPS (100 mu g) incr eased in vivo dopamine (DA) efflux from the nucleus accumbens, a region tho ught to be involved in goal-directed responding to positively reinforcing s timuli. It is suggested that LPS alters ICSS in a manner different than tha t observed following stressor exposure or peripheral IL-2 treatment. Furthe rmore, LPS may engender an anhedonic effect (possibly secondary to sickness ), and the decline of responding reflects the relation between the cost of responding given in the face of sickness and the reward received for respon ding. NeuroReport 9: 3797-3802 (C) 1998 Lippincott Williams & Wilkins.