Evidence that cyclic nucleotides are not mediators of fever in rabbits

1 The N6-2'-0-dibutyryl derivative of adenosine 3',5'-monophosphate (db cyclic AMP) and related compounds have been micro-injected into the preoptic/anterior hypothalamic nuclei (PO/AH) of the unanasthetized, restrained rabbit and the effects on deep body temperature observed. 2 Db cyclic (100-400 μg) produced hypothermia of rapid onset in rabbits at an ambient temperature of 20-23° C. Hypothermia was also produced by N2-2'-0-dibutyryl guanosine 3',5'-monophosphate (db cycle GMP), but not by saline, sodium n-butyrate, adenosine 3',5'-monophosphate (cylic AMP), guanosine 3',5'-monophosphate, adenosine 5'-mono-, di-, or triphosphate. 3 The initial hypothermic response to db cyclic AMP and db cylic GMP was followed by a sustained rise in temperature. However, all compounds injected into the PO/AH produced a similar hyperthermia which was attenuated by paracetamol. Development of this tissue-damage fever abolished the hypothermic response to db cyclic AMP in some rabbits. 4 The effects of db cyclic AMP on body temperature and behaviour were not reproduced by adenylate cyclase activators, cholera toxin (0.125-5 μg) and guanyl imidodiphosphate (5-400 μg). 5 It is concluded that hypothermia is the principal effect of db cyclic AMP on body temperature when injected into the PO/AH in rabbits. These data do no support the proposal that endogenous cyclic AMP in the rabbit brain mediates pyrexia.