In the present study we observed that
lipopolysaccharide (LPS) administration provoked a characteristic reduction in
body weight gain, food consumption,
saccharin (but not water) consumption and nocturnal locomotor activity. It has been previously suggested that the ability of LPS to suppress the consumption of, and preference for, a palatable
solution such as
saccharin without altering water consumption, may represent an anhedonic response. The results of the present study demonstrate that chronic treatment with the
tricyclic antidepressant (TCA)
desipramine (7.5 mg/kg; i.p.) prevented LPS-induced
anorexia, loss of
body weight, the antidipsogenic effect and hypoactivity. 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
desipramine (and to a lesser extent
paroxetine) reduced the consumption of, and 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 symptoms in the rat. However, chronic treatment with
paroxetine and
venlafaxine did not significantly alter LPS-induced behavioural responses. The results 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
antidepressants which possess a better side effect profile than the TCA's. The suppressive effect of TCA's on proinflammatory
cytokine secretion is discussed as a mechanism by which these agents alter LPS-induced behavioural responses.