The effect of various amine-depleting drugs on the fever response exhibited by rabbits to bacterial or leucocyte pyrogen

Abstract

1 The concentration of noradrenaline, dopamine and 5-hydroxytryptamine (5-HT) in the rabbit brainstem was measured during fevers produced by either an injection of bacterial pyrogen (BP) or continuous infusion of leucocyte pyrogen (LP). 2 Both procedures had little effect on the concentration of noradrenaline in the preoptic/hypothalamic area but significantly (P smaller than 0.001) lowered the concentration of noradrenaline in the midbrain and pons/medulla. 3 BP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the preoptic/hypothalamic area but had no effect in the midbrain or pons/medulla, whereas LP significantly (P smaller than 0.01) lowered the concentration of 5-HT in the midbrain and pons/medulla but had little effect in the hypothalamus. 4 The concentration of dopamine throughout the brainstem was little affected by either BP or LP fevers. However the concentration in the midbrain was significantly reduced by LP (P smaller than 0.001). 5 Alpha-Methyltyrosine (200 mg/kg) pretreatment diminished the pyrogenic response to both BP and LP whilst p-chlorophenylalanine (300 mg/kg) slightly enhanced the response to both forms of challenge. 6 Reserpine (1 mg/kg) diminished both types of fever whilst a combination of alpha-methyltyrosine and p-chlorophenylalanine slightly enhanced the fevers produced by either BP or LP. 7 The results obtained are discussed in relation to the mechanisms involved in the production of fever and to the possible function of noradrenaline and 5-HT as thermoregulatory transmitters.