Ligand anti-receptor study

Acute inhibition of IL-lp by means of the IL-1 receptor antagonist (which is also an endogenous ligand of the IL-1 receptors), the soluble IL-1 receptor, or substances that inhibit IL-1 production is followed by decreases in spontaneous sleep (reviewed in Refs. 40,46). TNF-a can also be inhibited by administering anti-TNF-a antibodies or soluble TNFRs, and these substances decrease spontaneous sleep (reviewed in Refs. 40,46). Inhibition of either IL-lp or TNF-a also attenuates sleep rebound after sleep deprivation (40,46). Further, suppression of TNF also blocks enhancements in NREM sleep in response to a mild increase in ambient temperature (67). NREM sleep is permanently reduced in mutant mice lacking type 1 IL-1 receptors, but interestingly, the decreases in NREM sleep occur during the active period of the day (68). Decreases in NREM sleep were found in mice with deficient 55-kD TNF receptor in one study (47) but sleep was normal in mice with the same defect in another experiment (69). 

The localization of DiB and D5 receptors by receptor binding autoradiography has been hampered by the lack of high affinity DiB/5 specific ligands. Therefore, in situ hybridization studies of the receptor mRNA and immunohistochemical studies with specific anti-D1B/5 antibodies have been used to map the distribution of D1B/5 receptors in the rat, monkey and human brain (Niznik et al., 2003). 

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