Interleukin-1β augments release of norepinephrine, dopamine, and serotonin in the rat anterior hypothalamus

We investigated the effects of interleukin-1β (IL-1β), administered directly into the rat anterior hypothalamus (AHY), on monoamine release in the same region by using a brain microdialysis technique and an HPLC- electrochemical detection system. First, to study the local effects of IL- 1β, we used a microdialysis probe equipped with a microinjection tube for administering IL-1β in the same region into which the probe had been inserted. IL-1β (1 ng) injected directly into the AHY elicited release of norepinephrine (NE), dopamine (DA), and 5-HT, as well as increases in their metabolites, 4-hydroxy-3-methoxyphenylglycol, 3,4-dihydroxy-phenylacetic acid, 4-hydroxy-3-methoxyphenylacetic acid, and 5-hydroxyindole-3-acetic acid, in the AHY. Vehicle alone exerted no effect on monoamine release. Although the elevated levels of NE and DA persisted for more than 6 hr after injection of IL-1β, the elevated levels of 5-HT were transient. Second, in order to investigate whether this effect of IL-1β is a direct action in the AHY, we performed in vitro experiments using hypothalamus slices. IL-1β (0.1 and 1 nM) increased the levels of each monoamine released from hypothalamic slices in a dose-dependent manner. These findings suggest that IL-1β acts directly on the hypothalamus to induce release of NE, DA, and 5-HT. Third, the roles of prostaglandins (PGs) in NE release in the AHY elicited by direct injection of IL-1β were examined. Indomethacin (INDO; 5 mg/kg) was administered intraperitoneally, and then 1 hr later, IL-1β (1 ng) was injected directly into the AHY through the microinjection tube. IL-1β was still capable of increasing NE release, although the INDO pretreatment had decreased 6-ketoprostaglandin F₁α levels in the rat hypothalamus. Fourth, to exclude the possibility that corticotropin-releasing hormone (CRH) is involved in NE release by IL-1β, rats were pretreated with dexamethasone (DXM; 0.3 mg/kg), and then NE release in the AHY elicited by IL-1β was measured. IL-1β was still capable of inducing NE release, although the DXM pretreatment had decreased blood adrenocorticotropic hormone levels. These findings suggest that IL-1β acts directly on the AHY to augment the release of NE without PG involvement or elevation of CRH levels.