Effects of kappa and delta opioid agonists on activity and thermosensitivity of rat hypothalamic neurons.
Extracellular recordings were made from 161 warm-sensitive, six cold-sensitive and 153 temperature-insensitive neurons in slices of the preoptic area/anterior hypothalamus (PO/AH) of rats, to investigate the effects of the kappa-receptor opioid agonist dynorphin A1-17 and the delta-receptor opioid agonist DPDPE on neuronal response characteristics. While 61% of the neurons exhibited kappa-receptors, delta-receptors were only present in 37% of the neurons. No co-localization was observed between kappa- and delta-receptors, whereas mu-receptors could be co-localized with kappa- as well as delta-receptors. Antagonistic effects on tonic activity were induced by different concentrations of the kappa-agonist dynorphin A1-17. At 0.5 nM, the excitatory effect was predominant, while 50% of the neurons were already inhibited at 5 nM and inhibition was the major effect at 100 nM. A significant increase in temperature sensitivity was observed in warm-sensitive neurons during administration of 0.5 nM dynorphin A1-17; in contrast, the temperature sensitivity was significantly decreased at the high dose of 100 nM. In most of the neurons responding to the delta-receptor agonist DPDPE (0.5-100 nM) the firing rate was decreased. The temperature sensitivity was only affected in warm-sensitive neurons, and was increased in the majority of neurons at 0.5 and 5 nM, but predominantly decreased at higher concentrations. The effects of low concentrations of dynorphin A1-17 and DPDPE were prevented by pre- and co-perfusion of the appropriate antagonists. The present results suggest that changes of the temperature sensitivity of warm-sensitive PO/AH neurons are an important mechanism for the effect of low doses of opioids on body temperature.
Yakimova
K S
KS
Department of Pharmacology, Faculty of Medicine,'Zdrave' 2 str., 1431 Sofia, Bulgaria.
Sann
H
H
Pierau
F K
FK
D000818:Animals; D004399:Dynorphins / Q000494:pharmacology; D004594:Electrophysiology; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007032:Hypothalamus, Anterior / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D011301:Preoptic Area / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology*
D004745:Enkephalins; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D004399:Dynorphins; D020881:Enkephalin, D-Penicillamine (2,5)-