GABAB 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 GABAB 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 GABAB 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 GABAB receptors resist acute desensitization to prolonged administration of baclofen (GABAB receptor agonist) in both presynaptic and postsynaptic compartments. The desensitization resistance of postsynaptic GABAB receptors was independent of presynaptic alteration and vice versa. The GABAB receptor-mediated inhibition at inhibitory presynaptic terminals also showed no desensitization. The results suggest that GABAB receptor-mediated inhibition remains functional in both postsynaptic and presynaptic compartments to sustained agonist administration in rat PAG neurons.