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Our recent results showed that angiotensin II or III (AII, AIII) microinjected into the zona incerta (ZI) significantly increased water intake. The most effective doses of AII and AIII were also defined. The two neuropeptides had their effects differently on drinking via different receptors. AII bound to AT(1) that was blocked by AT(1) receptor antagonist Losartan and the effect of AIII was eliminated by prior application of AT(2) receptor antagonist PD 123319. After different hydrational challenges, the effects of AII and AIII in the ZI have never been experimented, however. In the present experiments, the previously defined effective doses of AII (100 ng) or AIII (200 ng) were microinjected into the ZI after different types of challenges: (1). lowered thirst motivation when animals ingested approximately 40% of their daily fluid need during the consequent 60-min-daily-drinking period before the injection, (2). 48-h water deprivation, (3). intracellular dehydration and (4). extracellular dehydration. In all of the cases, incertally injected AII increased the animals' water ingestion. While Losartan could block these effects, PD 123319 was ineffective. Experiments were repeated by AIII, but in none of the cases differences were experienced between the groups. The finding that following hydrational challenges water intake increased only after AII injections and it could be blocked only by Losartan suggests that AII and AT(1) receptor play a pivotal role in the ZI in maintaining the body water balance.

Different doses of angiotensin II (AII) or angiotensin III (AIII) microinjections into the zona incerta have been studied on drinking of rats in separate experiments during the consequent 60-min-daily-drinking period. Also, the dipsogen power of only the effective dose of AII and AIII was compared to vehicle treated rats. After, angiotensin receptor (AT(1), AT(2)) antagonists on AII or AIII induced drinking were tested. In the first and second experiments only the 100 ng AII and the 200 ng AIII increased water intake significantly. In the third experiment the AII started its dipsogen effect earlier, at the 5 min measuring time, compared to the AIII. Both effects kept on lasting parallel from the 10 min on. Considering the antagonist pre-treatments in the fourth experiment, animals were injected with 90 ng losartan, an AT(1) antagonist, 180 ng PD 123319 or 200 ng CGP 42112, both AT(2) antagonists, respectively. Both AII and AIII increased water consumption. The effect of AII could be blocked by losartan, but not by PD 123319 or CGP 42112. On the other hand, the effect of AIII could not be blocked by losartan, but by both the PD 123319 and CGP 42112. Since, the effects of AII, AIII and angiotensin antagonists have not been tested in the zona incerta, the finding that water intake increased after AII or AIII injections and it could be blocked only by either of the antagonists suggests that AT(1) and AT(2) receptors play partially different roles in the regulation of water intake.

Extracellular single-unit recordings were made from neurons in the lateral hypothalamus (LH) or zona incerta (ZI) of conscious sheep. A small population of neurons (12/83) were found which responded with increased firing rate when the animal looked at food but did not respond when the sheep looked at water. The effects of rapidly inducing intense thirst by the intracerebroventricular (i.c.v.) injection of hypertonic (0.85 M) saline or 200 ng of angiotensin II, or a mixture of the two dipsogenic stimuli, on the response of neurons initially responding only to the sight of food were investigated. Following i.c.v. injection of the dipsogenic stimuli the neurons began to respond strongly to the sight of water. The results demonstrated that changing the animal's motivational state alters the response of some neurons in the LH and ZI and suggests that the neuronal response is influenced by the animal's dominant need at the time of testing.

We investigated whether stimulation of the functionally discrete subthalamic region, subthalamic cerebrovasodilator area (SVA), which increases cerebral blood flow (CBF) when excited, would, like stimulation of cerebellar fastigial nucleus (FN), produce central neurogenic neuroprotection. A 1-h electrical stimulation of SVA or FN reduced infarctions triggered by permanent occlusion of middle cerebral artery (MCA) by 48-55% in Sprague-Dawley rats and by 59% in Fisher rats. The salvaging effect of SVA stimulation, similar to FN, was long lasting and reduced the volume of infarctions placed 72 h or 10 days later by 58 and 26%, respectively, in Fisher rats. Bilateral lesioning of FN neurons by the microinjection of ibotenic acid 5 days before SVA stimulation did not affect SVA-evoked neuroprotection. Bilateral lesions of SVA neurons administered 5 days before FN stimulation had no effect on FN-induced neuroprotection but reversed the stimulus-locked increase in CBF accompanying FN stimulation. This study demonstrates that (1) excitation of neurons and/or fibers projecting through the SVA reduces ischemic infarctions as substantially as excitation of FN neurons; (2) the effects are long-lasting and not attributable to increases in cerebral blood flow, changes in blood gases or brain temperature, or rat strain; (3) the neuroprotective effects of SVA and FN stimulation are mutually independent and (4) FN-evoked cerebrovasodilation is mediated by SVA neurons. The SVA and FN are part of a neuronal system in CNS, which is distributed and, when excited, acts to protect the brain from ischemic injury.