Adenosine in the lateral hypothalamus/perifornical area does not participate on the CO2 chemoreflex.

The Lateral Hypothalamus/Perifornical Area (LH/PFA) has been shown to be involved with the hypercapnic ventilatory response, in a state-dependent manner. We have demonstrated that purinergic signaling through ATP in the LH/PFA has an excitatory effect in ventilatory response to CO2 in awake rats in the dark phase of the diurnal cycle, but it is unknown whether the ATP metabolite adenosine, acting in the LH/PFA, modulates the ventilatory responses to hypercapnia. Here, we studied the effects of the microdialysis of adenosine (A1/A2 adenosine receptors agonist; 17 mM) and an A1 receptor antagonist (DPCPX; 0.1 mM) into the LH/PFA of conscious rats on ventilation in room air and in 7% CO2 during the light and the dark phases of the diurnal cycle. The microdialysis of adenosine and DPCPX caused no change in the CO2 ventilatory responses of rats during wakefulness or NREM sleep in either the dark or light period. Our data suggest that adenosine in the LH/PFA does not contribute to the hypercapnic ventilatory response in conscious rats.

Glutamate metabotropic receptors in the lateral hypothalamus/perifornical area reduce the CO2 chemoreflex.

It has been shown that the lateral hypothalamus/perifornical area (LH/PFA) exerts an important role on arousal-state variations of the central chemoreflex, but the mechanisms that underlie LH/PFA chemoreception are poorly understood. Here we asked whether glutamate inputs on metabotropic receptors in the LH/PFA modulate the hypercapnic ventilatory response. We studied the effects of microinjection of a glutamate metabotropic receptor (mGluR) antagonist ((+)-α-Methyl-4-carboxyphenylglycine; MCPG; 100 mM) and a selective Group II/III mGluR antagonist ((2S)-2-Amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid; LY341495; 5 mM) into the LH/PFA of conscious rats on ventilation in room air and in 7% CO2, during wakefulness and sleep, in the dark and light periods of the diurnal cycle. Microinjection of MCPG and LY341495 increased the hypercapnic ventilatory response in both the light and the dark period during wakefulness, but not during sleep, (p < 0.001). Our data suggest that glutamate, acting on Group II/III metabotropic receptors in the LH/PFA, exerts an inhibitory modulation of the hypercapnic ventilatory response in awake rats.