Sleep induction and temperature lowering by medial preoptic alpha(1) adrenergic receptors

Changes in sleep-wakefulness (S-W) and body temperature (T(b)) on administration of alpha(1) agonist (methoxamine) and antagonist (prazosin) into the medial preoptic area (mPOA) were studied in rats. Presynaptic catecholaminergic terminals of the mPOA were destroyed by injecting 6-hydroxydopamine at the ventral noradrenergic bundle (VNA), before administration of the drugs. Microinjection of 0.05 microg methoxamine induced sleep, though 0.1 microg prazosin produced no change in S-W. On the other hand, in normal rats, the same dose of methoxamine produced no change, while prazosin produced arousal. Denervation hypersensitivity may be responsible for the appearance of hypnogenic response on methoxamine administration, in the VNA-lesioned rats. The VNA-lesioned animals (before administration of any drug) had higher pre-injection values of wake period than the normal rats. A reduction in the tonic activity of noradrenergic fibers to the mPOA, and resulting reduced activity of alpha(1) receptors, may be responsible for increased wake period in the VNA-lesioned rats. The action of prazosin was probably abolished in the absence of tonic activity of alpha(1) receptor in the VNA-lesioned rats. Reduction and increase in T(b) produced by methoxamine and prazosin, respectively, confirm the involvement of alpha(1) receptors in the thermal changes. Methoxamine was less effective, than in normal rats, in reducing T(b). So, the possibility of involvement of presynaptic receptors in the thermal response is suggested. The results suggest the involvement of separate sets of alpha(1) receptors (and neurons) in hypnogenesis and in lowering T(b). As sleep is associated with fall in T(b), the alpha(1) adrenergic receptors may be involved in interlinking sleep regulation and thermoregulation.