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.