Generation of a physiological sympathetic motor rhythm in the rat following spinal application of 5‐HT

Abstract

When applied in vitro to various CNS structures 5-HT and/or NMDA have been observed to generate rhythmic nervous activity. In contrast, reports of similar in vivo actions are relatively rare. Here we describe a physiological sympathetic motor rhythm regulating the thermoregulatory circulation of the rat tail (T-rhythm; 0.40-1.20 Hz) that can be elicited following intrathecal (I.T.) application of 5-HT to an in situ 'isolated' spinal cord preparation (anaesthetized rats spinalized at T10-T11 and cauda equina cut). I.T. injections were delivered to L1 as sympathetic neuronal activity to the tail (SNAT) arises from preganglionic neurones at T11-L2. SNAT was abolished after spinal transection (n = 18) and it did not return spontaneously. The administration of 5-HT (250 nmol) generated rhythmic sympathetic discharges (n = 6). The mean frequency of the T-like rhythm during the highest level of activity was 0.88 ± 0.04 Hz which was not significantly different from the T-rhythm frequency observed in intact animals (0.77 ± 0.02 Hz; P > 0.05 n = 16). In contrast, NMDA (1 μmol) generated an irregular tonic activity, but it failed to generate a T-like rhythm (n = 9), even though the mean levels of activity were not significantly different to those produced by 5-HT. However, 5-HT (250 nmol) applied after NMDA generated a T-like rhythm (0.95 ± 0.11 Hz, n = 6). Our observations support the idea that 5-HT released from rostral ventromedial medullary neurones, known to innervate sympathetic preganglionic neurones, can induce sympathetic rhythmic activity.

Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction

“…These results are consistent with the earlier demonstration that GABA into the ventromedial medulla, including the rRPa, abolished spontaneous SNA to the rat tail, but only attenuated the increased tail SNA evoked by intracerebroventricular administration of PGE 1 (18). Spinal administration of serotonin can evoke increases in rat tail SNA after spinal transection (25) and blockade of spinal serotonin receptors attenuates evoked sympathetic outflow to the cutaneous vessels in the rabbit ear (39). Nanoinjection of serotonin into the spinal intermediolateral nucleus produces a long-lasting potentiation of NMDA-evoked increases in BAT SNA, even at doses of serotonin that are subthreshold for evoking increases in BAT SNA (24).…”

Selective blockade of 5-HT2A receptors attenuates the increased temperature response in brown adipose tissue to restraint stress in rats

“…Thus it is most likely that SR-46349B attenuated restraint stressinduced tail vasoconstriction by blocking 5-HT2A receptors located on the relevant sympathetic vasomotor neurons in the spinal cord. This is in accord with a recent report that intrathecal injection of serotonin increases activity in rat tail sympathetic nerves (Marina et al 2006). It must be acknowledged that at the highest dose, SR-46349B nearly completely abolished stress-induced cutaneous vasoconstriction whereas the increase in the iBAT temperature was attenuated by only about 50%, suggesting involvement of some other receptors.…”

Multiple thermoregulatory effectors with independent central controls

“…The idea that this synapse might be a subsidiary site, where humoral factors such as prostaglandin E 2 might act on several pathways at once to cause fever, received no experimental support (Tanaka and McAllen 2005). A further point that deserves consideration is that the abundant serotonergic neurons in this region, whilst they may not constitute the primary drive pathway for thermogenesis or vasoconstriction (Nakamura et al 2004), nevertheless, could play a modulatory role that reinforces several cold-defence responses at a spinal level Marina et al 2006). Serotonergic neurons in this region are activated by cold exposure (Yang et al 2000;Nakamura et al 2004) and may receive their temperature-related signals directly or indirectly from the preoptic area.…”