Behavioral and neuroendocrine responses in mice in which the locus coeruleus (LC) was ablated selectivly by the immunotoxin

Abstract

We reported a novel mouse model in which the LC noradrenergic (NA) neurons were ablated selectively, leaving other NA cell groups intact. Transgenic mouse was used that expressed human interleukin-2 receptors (hIL2R) under the promoter of dopamine-β hydroxylase. The hIL2R was colocalized with tyrosine hydroxylase (TH) immunoreactivity in anatomically defined NA neurons. The hIL2R was identified in the cell bodies and dendrites but not in axons. The immunotoxins (conjugates of antibody against hIL2R and Pseudomonas exotoxin) was injected into bilateral LC. The LC cells disappeared at day 7 following the immunotoxin injection, and did not regenerate at day 28. The TH-immunoreactive axon terminals decreased remarkably in brain regions receiving NA inputs exclusively from the LC. Ambulatory behaviors (elevated plus-maze and open field exploration) were analyzed by the software developed in our laboratory. The number of marbles buried, as well as the light/dark transition, was assessed. Overall, the levels of anxiety decreased in the LC-ablated mice in comparison with the controls. However, plasma ACTH levels were not affected following the restraint stress or LPS-induced immune challenge. The results suggest the involvement of the LC in anxiety-like behavior but not in neuroendocrine stress responses in mice. [J Physiol Sci. 2008;58 Suppl:S57]