Intrapreoptic microinjection of TNF-α enhances non-REM sleep in rats

Tumor necrosis factor-alpha (TNFalpha) is involved in sleep regulation. Peripheral or central administration of TNFalpha induces non-rapid eye movement sleep (NREMS) in many species. However, the brain site responsible for TNF-enhanced NREMS remains unclear. Thus, we tested the hypothesis that the preoptic area (POA) of the anterior hypothalamus. a crucial site for sleep regulation, is involved in TNF-induced sleep responses in rats. Unilateral microinjection of TNFalpha (2, 20 and 100 ng) or a TNF receptor fragment (TNFRF; 1.25, 5.0 and 12.5 mug) into the POA was performed at dark onset and light onset, respectively. The two higher doses of TNFalpha increased NREMS and brain temperature with little effect on REMS and EEG slow wave activity. These effects were lost after the heat-treatment of TNFalpha. The two higher doses of the TNFRF decreased NREMS without affecting the other parameters measured. Combined with previous results showing diurnal variations of TNFalpha in the hypothalamus. the present data suggest that POA TNFa is involved, in part, in the regulation of physiological sleep. (C) 2002 Elsevier Science B.V. All rights reserved.