Involvement of carbon monoxide in modulation of emotional behavior in endotoxemic rats.

Abstract

The carbon monoxide (CO) is a neuromodulator gas which may be involved in apoptosis, cellular proliferation, inflammation and the emotional behavior, for instance, the anxiety modulation. The CO can act on the anxiety in a process dependent of kinase protein C which is activated by soluble guanylate cyclase and 3'-5'-guanosine monophosphate. This mechanism can modulate noradrenergic neurons in locus coeruleus (LC) which does projections to neural substrates, such as hippocampus, amygdala and hypothalamus. These structures are involved in the modulation of emotional behavior, and previous studies showed that the heme-oxygenase (HO)-CO pathway regulated the anxiety in healthy animals. Therefore, we will evaluate if the HO-CO pathway regulates the anxiety in endotoxemic rats induced by Lipopolysaccharide (LPS). The cytokine levels (IL-6, IL-1² e TNF±) will be measured, since they can cause adaptive response for example, fever and anxiety which are associated with the sickness behavior. It will be administrated ZnDPBG (HO enzyme inhibitor) and LPS in rats, which will be submitted to behaviors tests such as, elevated plus maze test, light-dark box and ultrasonic vocalization. The noradrenaline levels will be assessed in vivo at the amygdala and hippocampus, as well as the body temperature these animals. We will perform immunolabeling trials for HO (1), FRA and hydroxylase tyrosine, just as, western blotting for noradrenaline transporter. In this way, we hope that this project can contribute to a better understanding of the mechanisms involved in the modulation of emotional and psychiatric disorders in healthy animals and during infectious processes. (AU)