Differential sensitivity of presynaptic and postsynaptic GABA B receptors in rat ventrolateral periaqueductal gray

The ventrolateral periaqueductal gray (PAG) in the midbrain plays a key role in the descending pain modulatory system. γ-Aminobutyric acid type B (GABA B) receptors belong to a metabotropic receptor subfamily and mediate both presynaptic and postsynaptic effects in PAG. It has been well documented that activation of GABA B receptors yields analgesia in some PAG subdivisions. In the present study, employing whole-cell patch-clamp recordings on acute rat PAG slices, we simultaneously monitored the responses of presynaptic and postsynaptic GABA B receptors. We found that the GABA B agonist, baclofen, exhibits less efficacy and potency at GABA B postsynaptic versus presynaptic receptors. This sensitivity bias may contribute to synapse homeostasis and implicate a novel pharmacotherapy treatment.