Effects of GABAB-agonist on rat hypothalamic neurons: functional antagonism with mu-receptor agonist

Extracellular and whole-cell patch clamp recordings were made from neurons in slices of the preoptic area/anterior hypothalamus (PO/AH) of rats, to investigate the effects of the GABA(B)-receptor agonist baclofen on neuronal response characteristics, as well as its interactions with mu-opioid receptor agonist PL-017 on the level of central temperature controller. Baclofen decreased tonic activity (firing rate) in all types of neurons, but increased temperature sensitivity (temperature coefficient, TC) in warm-sensitive neurons. The decrease in firing rate during baclofen application was accompanied with significant membrane hyperpolarization and decrease of input resistances. The tonic activity (in all type of PO/AH neurons), as well as the temperature sensitivity (in warm-sensitive neurons), were inhibited by mu-opioid receptor agonist PL-017. Remarkably, the effect on temperature sensitivity was abolished and absence of synergism in regard to firing rate decrease occurred, when baclofen and PL-017 were applied simultaneously. Our results are step of understanding the complicated mechanisms of action of neurotransmitters and their interactions on the level of central temperature controller-the neurons of the PO/AH.