GABA_B receptors resist acute desensitization in both postsynaptic and presynaptic compartments of periaqueductal gray neurons

The ventrolateral midbrain periaqueductal gray (PAG) neurons have been intensively studied because of their pivotal role in the descending pain modulation system. Activation of GABA_B receptors, one type of inhibitory G-protein-coupled receptors (GPCRs), in PAG neurons results in both presynaptic and postsynaptic inhibition. Acute desensitization is defined as rapid attenuation of receptor-mediated signaling. Recent studies report that multiple inhibitory GPCRs, including GABA_B receptors, resist acute desensitization in the presynaptic but not postsynaptic compartments of certain neurons in mammal brains. In the present study, employing whole-cell voltage-clamp recordings on acute PAG slices from adult rats, we found that GABA_B receptors resist acute desensitization to prolonged administration of baclofen (GABA_B receptor agonist) in both presynaptic and postsynaptic compartments. The desensitization resistance of postsynaptic GABA_B receptors was independent of presynaptic alteration and vice versa. The GABA_B receptor-mediated inhibition at inhibitory presynaptic terminals also showed no desensitization. The results suggest that GABA_B receptor-mediated inhibition remains functional in both postsynaptic and presynaptic compartments to sustained agonist administration in rat PAG neurons.