The effect of the antipsychotic drug quetiapine and its metabolite norquetiapine on acute inflammation, memory and anhedonia

摘要

The atypical antipsychotic drug, quetiapine, has recently been suggested to not only show efficacy in schizophrenia, bipolar, major depressive and general anxiety disorders, but to also have a possible anti-inflammatory effect, which could be important in the treatment of the inflammatory aspects of psychiatric diseases. Male C578L/6 mice were given either quetiapine (i.p. 10 mg/kg), its main active metabolite norquetiapine (i.p. 10 mg/kg), or saline as a vehicle control, once a day for 14 days. On the 14th day, this dose was followed by a single dose of either LPS (i.p. 1 mg/kg) or saline. 24 h post LPS short-term recognition memory and anhedonia behaviour were measured using the Y-maze and saccharin preference test respectively. Immediately following behavioural testing, mice were culled before serum, prefrontal cortex and hippocampal analysis of cytokine levels was conducted. It was found that LPS challenge led to increased serum and brain cytokine levels as well as anhedonia, with no significant effect on recognition memory. Quetiapine and norquetiapine both increased levels of the anti-inflammatory cytokine IL-10 and decreased levels of the pro-inflammatory cytokine IFN-gamma in serum 4 h post LPS. Within the brain, a similar pattern was seen in gene expression in the hippocampus at 4 h for Il-10 and Ifn-gamma, however norquetiapine led to an increase in Il-1 beta expression in the PFC at 4 h, while both drugs attenuated the increased Il-10 in different regions of the brain at 24 h. These effects in the serum and brain, however, had no effect on the observed LPS induced changes in behaviour. Both quetiapine and its metabolite norquetiapine appear to have a partial anti-inflammatory effect on IL-10 and IFN-gamma following acute LPS challenge in serum and brain, however these effects did not translate into behavioural changes. (C) 2015 Elsevier Inc All rights reserved.