Differential sensitivity to the wake-promoting actions of norepinephrine within the medial preoptic area and the substantia innominata

Mapping studies were conducted to delineate the site(s) of action for the arousal-enhancing actions of norepinephrine (NE) within the basal forebrain region encompassing the medial preoptic area (MPOA) and the substantia innominata (SI). Varying doses of NE, the beta -agonist, isoproterenol, or the alpha (1)-agonist, phenylephrine, were infused into the MPOA or SI in the resting rat. Infusions of NE (4 nmol, 16 nmol/150 nl), isoproterenol (15 nmol/150 nl), and phenylephrine (40 nmol/250 nl) into the MPOA elicited robust increases in waking. In contrast, neither isoproterenol or phenylephrine infusions into the SI altered behavioral state. NE infusions into the SI increased waking only at the highest dose, and at this dose there was an anatomical gradient for NE-induced waking, with infusions placed farther from the MPOA, producing smaller increases in waking. Thus, in contrast to the MPOA, the SI is relatively insensitive to the wake-promoting actions of NE.