Effect of chronic treatment with perazine on lipopolysaccharide-induced interleukin-1β levels in the rat brain

Abstract

In the present study, we sought to determine whether chronic treatment with perazine alters lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1 beta) levels in the following rat brain regions: the hypothalamus, frontal cortex, striatum and hippocampus. Male Wistar rats were administered perazine dimaleate (15 or 30 mg/kg/day) in drinking water for 21 days. On day 22, LPS was injected i.p. (125 microg/kg) 2 h before decapitation. Concentrations of perazine and its metabolites in plasma and brain was assessed by HPLC. The levels of IL-1 beta were determined using ELISA. Treatment with perazine (30 mg/kg/day) reduced LPS-stimulated IL-1 beta levels in the hypothalamus, and a tendency to its decrease in the striatum and frontal cortex was observed. This in vivo study suggests for the first time that long-term oral administration of perazine modulates reactivity of cells producing IL-1 beta.

Repeated Lipopolysaccharide (LPS) or Cytokine Treatments Sensitize Ethanol Withdrawal-Induced Anxiety-Like Behavior

“…Likewise, the repeated IL-1b and TNF-a/withdrawal protocols induced an anxiety-like behavioral response upon withdrawal following a similar 16-day delay in re-exposure to chronic ethanol diet. This latter observation suggests that the persistent adaptation observed with the LPS/withdrawal protocol depends upon its influence on cytokines (Munhoz et al, 2006;Obuchowicz et al, 2006).…”

“…Likewise, LPS exposure in the absence of the chronic ethanol exposure did not affect this measure of anxiety-like behavior. As LPS is known to increase cytokines in brain (Grinevich et al, 2001;Hagan et al, 1993;Hillhouse and Mosley, 1993;Ilyin et al, 1998;Matalka et al, 2005;Munhoz et al, 2006;Obuchowicz et al, 2006;Quan et al, 1994;Zujovic et al, 2001), it was speculated that the ability of the repeated LPS exposure to Figure 5 Persistent effect of repeated IL-1b, TNFa, or LPS on withdrawal-induced anxiety following re-exposure to 5 days of chronic ethanol starting 16 days later. Subgroups of rats from Figures 2 and 3 were treated with an additional 5 days of ethanol diet (4.5%) 16 days after having been exposed earlier to the initial repeated LPS or to the cytokines TNFa or IL-1b.…”

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

“…Acute doses of other antipsychotics such as clozapine have been shown to inhibit LPS-induced TNF production in brains of mice (Mengozzi et al, 1994), while acute risperidone was able to prevent an increase in inflammatory parameters, including increased expression of Il-1β and Tnf-α, while also restoring anti-inflammatory pathways in the cortex of rats (MacDowell et al, 2013). Perazine treatment in drinking water for 21 days was also able to prevent the LPS-induced increase of IL-1β protein levels in the hypothalamus, striatum and frontal cortex, but not hippocampus in mice (Obuchowicz et al, 2006). These results differ from ours, in that we did not see any effect of quetiapine or norquetiapine on Tnf-α in the brain; however we saw an increase in Il-1β following norquetiapine pretreatment.…”

Comparison of behavioral, neuroprotective, and proinflammatory cytokine modulating effects exercised by (+)‐cis‐EC and (−)‐cis‐EC stereoisomers in a PTZ‐induced kindling test in mice

“…The parameters evaluated from which the scores were generated were as follows: Normal‐appearing neurons, that is, with clear nuclear contours with nucleoli present; Cell death, due to necrosis or apoptosis; Presence of inflammatory process being the presence of inflammatory cells, Edema. When one of these features was present, we added one to the score, totaling four, if all such injuries were found .…”