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.
Yakimova
Krassimira S
KS
Department of Pharmacology, Faculty of Medicine, Medical University, Sofia, Bulgaria. kyakim@medfac.acad.bg
D000200:Action Potentials; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001833:Body Temperature Regulation; D004723:Endorphins / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D007032:Hypothalamus, Anterior / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D011301:Preoptic Area / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000502:physiology; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000502:physiology; D013696:Temperature
D004723:Endorphins; D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D017450:Receptors, Opioid, mu; C044708:morphiceptin, N-Me-Phe(3)-; D001418:Baclofen