Noradrenaline inhibits preoptic sleep-active neurons through alpha 2-receptors in the rat

Effects of noradrenaline (NA) on the activity of sleep-related neurons in the preoptic area (POA) and the neighboring basal forebrain were examined in the rat. Of 36 sleep-active neurons tested, 19 were inhibited and the other 17 were unaffected by NA applied through a multibarrel pipette. The alpha 2-agonist clonidine inhibited 11 of 14 sleep-active neurons and did not affect the other 3 neurons, whereas the alpha 1-agonist methoxamine (n = 13) and the beta-agonist isoproterenol (n = 11) had no effect on any of the sleep-active neurons tested. Thus, alpha 2-receptors mediated the NA-induced inhibition. Of 22 waking-active neurons tested, NA excited 10, inhibited 1, and had no effect on the remaining 11. Methoxamine excited 4 of 13 waking-active neurons tested, whereas isoproterenol (n = 9) and clonidine (n = 4) were without effect on any of the waking-active neurons tested. Accordingly, alpha 1-receptors probably mediated the NA-induced excitation. Seventy-seven state-indifferent neurons, which lacked activity related to the sleep-waking state, and 20 paradoxical sleep-active neurons were mostly (65%-70%) insensitive to NA. These results suggest that NA promotes wakefulness by inhibiting sleep-active neurons and by exciting waking-active neurons.