The thermoregulatory effects of noradrenaline, serotonin and carbachol injected into the rat spinal subarachnoid space

Abstract

SUMMARY1. We have examined the effects on thermoregulation in the rat of noradrenaline bitartrate (NA), 5-hydroxytryptamine hydrochloride (5-HT) and carbamylcholine chloride (CCh) injected into the lumbar spinal subarachnoid space via a chronic indwelling catheter.2. Intrathecal injections of the monoamines and CCh reproducibly affected thermoregulation, whereas injections of control solutions had no effect.3. Intrathecal injections of NA (001-030 smol) produced a dose-dependent hypothermia associated with a decrease in tail skin vasomotor tone. Shivering activity was not depressed during the hypothermia and sometimes increased.Intrathecal administration of the a-adrenergic agonist clonidine (00175-0070 Itmol) elicited changes in Tc and Tsk similar to those induced by intrathecal NA.4. Intrathecal 5-HT (0030-090 ,mol) elicited a dose-dependent hyperthermia accompanied by increased tail skin vasomotor tone and increased shivering.5. CCh injected intrathecally (0001-0406 #smol) evoked a dose-dependent hyperthermia. During the period when core temperature was rising, tail skin vasomotor tone increased and shivering-like activity was present. Once the maximum core temperature had been reached, tail skin vasodilatation occurred. Vasodilatation persisted until core temperature had returned to normal.6. Intravenous injections of 5-HT (030 and 090 /smol) or CCh (0006 and 003 tmol) caused no thermoregulatory effect. The effects of these agents injected intrathecally were therefore not due to an action in the periphery.7. Intravenous infusions of NA (006 and 0 10 smol) produced hypothermia and transient tail skin vasodilatation. We suggest that an action at peripheral sites may have contributed to the effects produced by intrathecal injection of this monamine.8. These findings suggest that spinal noradrenergic, serotonergic and cholinergic synapses may be importantly involved in the control of body temperature in the rat. The possible functional roles of these synapses and the putative spinal sites of action of the injected substances are discussed. R. M. LOPACHIN AND T. A RUDY

Sites and mechanism of action for the effects of intrathecal noradrenaline on thermoregulation in the rat

“…is known to cause a fall in TR (Clark &-Clark, 1980), the possibility that intrathecally injected NA caused hypothermia by diffusion to supraspinal sites of action could not be ruled out. Moreover, intravenous infusions of0 10 mole NA produced thermoregulatory effects qualitatively similar to those elicited by intrathecal injection of 0 30 molel, although the tail skin vasodilation was much shorter and the hypothermia significantly smaller (LoPachin & Rudy, 1982). Therefore, it was thought possible that a portion of the hypothermic and vasodilatory effects and perhaps all of the hyperthermic effect of NA were a consequence of an action, in the periphery, of NA which had leaked from its subarachnoid site of injection into the systemic circulation.…”

“…by f-blockade) caused a fall in rat body temperature (Stoner, 1973;Horwitz & Hanes, 1976). Moreover, evidence was presented in a previous publication (LoPachin & Rudy, 1982) suggesting that intrathecal injection of NA can inhibit non-shivering thermogenesis.…”

“…The experiments described in this report constitute an extension ofa previous study in which the thermoregulatory effects of noradrenaline (NA) injected into the spinal subarachnoid space of the rat were investigated (LoPachin & Rudy, 1982). In that report, it was noted that intrathecal injections of NA in the dose range of 0-01-O)10 molee produced a dose-dependent fall in core temperature (TR) which was associated with a rise in tail skin temperature (0k).…”

“…We have suggested elsewhere (LoPachin & Rudy, 1982) that the fall in core temperature produced by intrathecal injection of NA (and also clonidine) might be mediated in part via an inhibition of sympathetic outflow. Certainly the tail skin vasodilation produced by intrathecal NA and clonidine is a physiological effect commensurate with the proposed sympatho-inhibitory action of these drugs.…”

“…Drug and control solutions were injected into the spinal subarachnoid space in a volume of 4 l1. Details of the injection procedure have been discussed in a previous paper (LoPachin & Rudy, 1982). The control solutions for the intrathecal injections of NA and clonidine are the same as those described by LoPachin & Rudy (1982).…”