Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat

In the present study we observed that lipopolysaccharide (LPS) administrati on provoked a characteristic reduction in body weight gain, food consumptio n, saccharin (but not water) consumption and nocturnal locomotor activity. It has been previously suggested that the ability of LPS to suppress the co nsumption of, and preference for, a palatable solution such as saccharin wi thout altering water consumption, may represent an anhedonic response. The results of the present study demonstrate that chronic treatment with the tr icyclic antidepressant (TCA) desipramine (7.5 mg/kg; i.p.) prevented LPS-in duced anorexia, loss of body weight, the antidipsogenic effect and hypoacti vity. In contrast, chronic treatment with the antidepressants paroxetine (7 .5 mg/kg; i.p.) and venlafaxine (10 mg/kg; i.p.) failed to alter any of the LPS-induced behavioural responses. Furthermore, chronic treatment with des ipramine land to a lesser extent paroxetine) reduced the consumption of, an d preference for, saccharin suggesting that these antidepressant treatments induce an "anhedonic" response in their own right. In conclusion, chronic desipramine treatment attenuated LPS-induced depressive-like behavioural sy mptoms in the rat. However, chronic treatment with paroxetine and venlafaxi ne did not significantly alter LPS-induced behavioural responses. The resul ts of the present study support the hypothesis that TCA's may exert part of their anti-depressive efficacy through their effects on the immune system. However, this property does not appear to be shared by newer antidepressan ts which possess a better side effect profile than the TCA's. The suppressi ve effect of TCA's on proinflammatory cytokine secretion is discussed as a mechanism by which these agents alter LPS-induced behavioural responses.