The
organophosphate pesticide (OP)
chlorpyrifos leads to an acute period of
hypothermia followed by a delayed
fever in the rat. Methyl
scopolamine, a peripheral
muscarinic antagonist, is thought to have little effect on body temperature of the rat because it does not cross the blood brain barrier. However, administration of methyl
scopolamine (1 mg/kg, i.p.) during the period of
chlorpyrifos-induced
fever results in a rapid recovery of core temperature. This indicates a peripheral
cholinergic pathway is operative in the febrile response to
chlorpyrifos and possibly other modes of
fever. In this study, we evaluated the possible
antipyretic role of methyl
scopolamine (i.p.) to a variety of stimuli that lead to
fever-like responses in the rat: stress-induced (handling and cage switch),
chlorpyrifos-induced (15 mg/kg, p.o.), nocturnal-induced, and
lipopolysaccharide (LPS)-induced
fever (50 microg/kg, i.p.). Methyl
scopolamine led to marked reversal in the elevated core temperature caused by handling, cage switch, and during the nocturnal phase. It is of interest to note that all these elevations of core body temperature are
prostaglandin mediated and are blocked with the
antipyretic drug,
sodium salicylate. However, LPS-induced
fever, also a
prostaglandin dependent
fever, was unaffected by methyl
scopolamine. Methyl
scopolamine also lowered baseline core temperature when administered during the afternoon, but not during the morning in unstressed animals. It is proposed that a peripheral
cholinergic pathway, possibly mediated through afferent vagal pathways, is operative in controlling core temperature during
fevers associated with stress, nocturnal phase, and a
pesticide. During recovery from exposure to a LPS, the
fever appears to be mediated independently of peripheral
cholinergic activation.