Responsiveness of rats to interleukin-1: effects of monosodium glutamate treatment of neonates.

Monosodium glutamate (MSG) treatment of neonatal rats results in degenerative lesions of the medial basal hypothalamus, particularly the arcuate nucleus (AN). The AN is rich in corticotropin-releasing hormone (CRF) and adrenocorticotrophic hormone/alpha-melanocyte-stimulating hormone (alpha-MSH). These substances are part of a negative feedback mechanism for the regulation of interleukin-1 (IL1), a cytokine with diverse biologic actions including a role in sleep regulation. The purpose of these experiments was to determine the effects of exposure of neonatal rats to MSG on their responsiveness as adults to IL1. Adult rats, treated as neonates with MSG or the saline, were injected intracerebroventricularly during the light phase with three doses of IL1 (2.5, 10.0, 25.0 ng) and sleep-wake activity determined and brain temperature recorded for the next 6 hr. IL1 administration induced fever in both treatment groups at each dose of IL1 tested, and the febrile response of the MSG rats to the 25.0 ng dose of IL1 was greater than that of the saline control rats. In saline-treated rats, the 2.5 ng dose of IL1 enhanced non-rapid-eye-movement sleep (NREMS) without affecting rapid-eye-movement sleep (REMS) or wakefulness, whereas the 25.0 ng dose of IL1 inhibited both NREMS and REMS. In contrast, only the 10.0 ng dose of IL1 altered NREMS in MSG-treated rats. These results support the hypothesis that CRF- and alpha-MSH-containing perikarya are involved in regulation of IL1 actions.