Noradrenaline neurotoxin DSP-4 effects on sleep and brain temperature in the rat

N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) has a selective degenerative effect on noradrenergic fibers originating from locus coeruleus (LC) neurons. In the present study, we studied its effect on vigilance states and brain temperature by continuous recordings for periods of 1-5 days and 2-4 weeks following DSP-4 treatment. On the first day, paradoxical sleep duration was significantly decreased (-67%, P < 0.05), slow-wave sleep (SWS) duration increased (+16%, P < 0.05) up to 48 h after DSP-4 treatment (+8%, P < 0.05) and the wake period decreased (-8%, P < 0.05). The vigilance states returned to control values 4-5 days later. The brain temperature was decreased during the first night (-2 degrees C) and then recovered the control values. Two and 4 weeks after DSP-4 treatment, paradoxical sleep was still decreased (-18% and -23%, respectively, P < 0.05), while SWS was significantly increased only at night during the fourth week (+23%, P < 0.05). These results therefore provide evidence for a differential involvement of the noradrenergic LC system in sleep mechanisms depending on the light-dark cycle. Different hypotheses are proposed.