ENDOTOXIN PRODUCES A DEPRESSIVE-LIKE EPISODE IN RATS

Activation of the immune system produces psychological and physiologic al effects, which resemble the characteristics of depression. The pres ent study was designed to investigate further, in rats, the similarity between the behavioral effects of immune activation and a model of de pression in animals. Reduction in the preference for and consumption o f saccharin solutions and suppression of sexual behavior were used as models of one essential feature of depression, the inability to experi ence pleasure (anhedonia). Other measures testing this model were the reduction in food consumption, body weight, locomotor activity, and so cial interaction. It was found that systemic injection of lipopolysacc haride (endotoxin), which is a potent activator of the immune system, significantly decreased saccharin preference in fluid-deprived rats. L ipopolysaccharide (LPS) also decreased free consumption of saccharin, but not water, in non-deprived rats. Several indices of male sexual be havior were significantly suppressed following LPS administration. Chr onic, but not acute, treatment with the tricyclic antidepressant imipr amine abolished the suppressive effect of LPS on saccharin preference. Moreover, chronic, but not acute, treatment with imipramine also redu ced and facilitated the recovery from the suppressive effects of LPS o n food consumption, body weight, social interaction and activity in th e open-field test. The results suggest that activation of the immune s ystem in rats produces anhedonia and other depressive-like symptoms, w hich can be attenuated or completely blocked by chronic treatment with an antidepressant drug.