Cuneiform nucleus stimulation-induced sympathoexcitation: role of adrenoceptors, excitatory amino acid and serotonin receptors in rat spinal cord.

Abstract

Stimulation of the midbrain cuneiform nucleus has previously been shown to produce increases in arterial blood pressure and lumbar sympathetic nerve activity. While this sympathoexcitatory effect is, in part, due to excitation of premotor sympathoexcitatory neurons in the rostral ventrolateral medulla, the specific spinal neurotransmitter systems recruited by cuneiform nucleus stimulation remains to be elucidated. In this study, mean arterial pressure, resting and cuneiform nucleus stimulation-evoked lumbar sympathetic nerve activity were analysed following intrathecal injections of an excitatory amino acid antagonist (kynurenic acid), alpha1-adrenoceptor antagonist (prazosin) and a serotonin receptor antagonist (methiothepin) in anesthetized, paralysed male Sprague-Dawley rats. Mean arterial pressure and resting sympathetic nerve discharge were decreased by all treatments (n = 6/group) compared to the vehicle control group. Intermittent electrical stimulation of the cuneiform nucleus produced a bimodal sympathoexcitatory response, of which the short latency peak was significantly attenuated (43% reduction) by intrathecal kynurenate whereas the long latency peak was reduced by intrathecal prazosin (decrease of 21%) and methiothepin (38% attenuation). These results are consistent with the significant roles of excitatory amino acid, alpha1-adrenergic and serotonin receptors in modulating the activity of sympathetic vasomotor preganglionic neurons supplying the lumbar sympathetic nerve trunk, and suggest the existence of at least three neuronal groups and/or pathways associated with the sympathoexcitatory response to cuneiform nucleus stimulation.