The effects of electrophoretically applied prostaglandin D
2 (PGD
2) on neuronal activity in the rat lateral preoptic area (LPOA) and posterior hypothalamic area (PHA) were examined. In the LPOA, 20% of the tested neurons were excited, 26% inhibited, and 6% showed bidirectional response. The direct effects often showed desensitization after repeated applications. Neurons excited by PGD
2 were significantly sensitive (excitation) to acetylcholine (ACh). The ACh excitatory effect was sometimes (38%) attenuated, blocked, or reversed by concurrent PGD
2 application. Excitatory or inhibitory effect of noradrenaline (NA) was not related to the effects of PGD
2, however, modulation of the NA responses by PGD
2 was common (58%). Inhibition, the predominant NA response, was changed to no effect or to excitation during simultaneous PGD
2 application. Changes of the NA responses from inhibition to excitation, or from excitation to inhibition-excitation sequences were observed after PGD
2 infusion into the third cerebral ventricle at low concentrations. In 43% of the cells, neurotransmission in the LPOA following ventral noradrenergic bundle stimulation was modified by PGD
2 application. PGD
2 application tended to reduce the duration of inhibition and to extend that of excitation. The direct effects of PGD
2 in the PHA were similar to those in the LPOA. Desensitization was also observed in the PHA, but no interrelations were observed among the effects of PGD
2, ACh, and NA. Modulation of ACh and NA responses by PGD
2 was rarely seen in the PHA. Possible contributions of PGD
2 to sleep and thermoregulation are discussed.
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