Abstract:

The administration of lipopolysaccharide (LPS), a component of the cell wall of gram negative bacteria, is commonly-used method to cause immune activation and the release of cytokines both in the periphery and in the brain in rodents. The cytokine theory of depression indicated that pro-inflammatory cytokines play an important role in the pathological mechanism of depression. Many studies used the peripheral administration of LPS to induce depressive-like behaviors. However, in these studies, the altered behaviors usually last only a few hours, seldom longer than 24h. Such short-term depressive behavior can hardly be regarded as a model of depression.. Thus, the aim of the present study was therefore to develop a new animal model of depression with apparent depressive-like behavior at - and after- 24h post-LPS injection. In this study, single and triple central LPS administration were used to induce depressive-like behavior respectively. Sprague-Dawley rats were randomly divided into LPS group and control group. LPS (100ng/rat, one injection; or once every second day, total three times) or isotonic saline was administered by intracerebroventricular microinjection. The depressive-like behavior was measured by preference to saccharin, locomotor activity and immobility time of tail suspension. The result indicated that single central LPS injection induced partial depressive-like behaviors. There was significant difference in locomotor activity, but not in the preference of saccharin and immobility time of tail suspension. However, repeated central LPS administration induced significant depressive-like behaviors after 24h of the last LPS injection. The animals with triple central LPS administration consumed less saccharin solution, exhibited less locomotor activity in the open field, and maintained immobility time in tail suspension. The changes in locomotor activity and immobility time of tail suspension were even apparent until 72h after the last LPS injection. Our results demonstrate that a new effective model of depression can be established by means of repeated lateral ventricle LPS injections, and the induced depressive-like behavior has longer time duration than by the peripheral injection of LPS.

Key words: New model of depression, Lipopolysaccharide, Central immune activation, Time duration