Enhanced expression of heme oxygenase-1 in the locus coeruleus can be associated with anxiolytic-like effects

Some researchers have shown that carbon monoxide (CO) plays a role in emotional behavior modulation through intracellular 3′-5′-guanosine monophosphate mechanisms in the locus coeruleus (LC). In fact, the LC region has a high expression of the heme-oxygenase (HO) enzymes, which are responsible for the production of CO. However, the physiological mechanism by which the HO-CO pathway participates in the modulation of emotional responses in the LC still needs clarification. This study evaluates whether a systemic intraperitoneal treatment is able to alter behavioral responses (in the elevated plus-maze and the light-dark box test) and the expression of the HO-1 and HO-2 enzymes in the LC. The tested treatments are acute (3 h before) or chronic (twice daily for 10 days) and with a carbon monoxide releaser (tricarbonyldichlororuthenium [II] dimer, or CORM-2) or with a HO-1 inducer compound (cobalt protoporphyrin IX, CoPP). The results for the elevated plus-maze show that CO-for both acute or chronic administration of either drug-ncreased the number of entries into the open arms and the percentage of time spent in the open arms. Regarding the light-dark box test, chronic treatment with either drug increased the time spent in the light compartment. Additionally, treatment with CORM-2 or CoPP, either acutely or chronically, increased HO-1 enzyme expression in the LC cells. This study shows that systemic CO treatment can promote an anxiolytic-like effect and the expression of HO-1 enzymes in LC cells.