Role of L-glutamate in the locus coeruleus of rats in hypoxia-induced hyperventilation and anapyrexia.

Locus coeruleus (LC) is a noradrenergic nucleus in the pons which has been reported to play an inhibitory role in the ventilatory response to hypoxia. Since LC contains glutamatergic receptors and L-glutamate is known to participate in the ventilatory and thermoregulatory responses to hypoxia, the effects of kynurenic acid (KYN, a glutamatergic receptor antagonist) microinjected into the LC in the hypoxic hyperventilation and anapyrexia (a regulated drop in body temperature [Tb]) were examined. Ventilation (V) and Tb were measured before and after a microinjection of KYN (10 nmol/0.1 microl) into the LC, followed by hypoxia. Control rats received a saline injection. Under normoxia, KYN treatment did not affect V or Tb. Typical hypoxia-induced hyperventilation and anapyrexia were observed after saline injection. KYN injection caused an increase in the ventilatory response, acting on tidal volume (Vt), but did not affect the anapyrexic response to hypoxia. These data suggest that L-glutamate in the LC is an excitatory neurotransmitter that activates an inhibitory pathway to reduce the hypoxic ventilatory response, similarly to the data reported for rostral ventrolateral medulla (VLM). The role of L-glutamate into the LC and VLM opposes its effect on other nuclei such as the nucleus of the solitary tract and ventromedullary surface, where the neurotransmitter participates in an excitatory pathway of the ventilatory response.