1 Kinin analogues bradykinin (BK), T-kinin, Met-Lys-BK, Lys-Lys-BK, Des-Arg9-BK with agonist activity and D-Arg0-Hyp3-This58-D-Phe7-BK (DAHTDBK) and Arg9-Leu8-BK with antagonist activity were injected into the posterior portion of the fourth cerebral ventricle of unanaesthetized rats implanted with permanent cannulae and arterial pressure was measured directly from the abdominal aorta. 2 The spontaneously hypertensive rats (SHR) were more sensitive than normotensive Wistar rats (NWR) to the pressor effect of BK and other kinin analogues. The SHR did not differ in sensitivity of the pressor response to centrally administered angiotensin II or endothelin-1. 3 Experiments with selective kinin agonists and antagonists revealed that in the SHR, as in the NWR, the receptors which mediated the central pressor response are of the BK2 subtype. 4 Measurements of the pressor activity of kinins with different degrees of susceptibility to degradation, as well as experiments with kininase inhibitors, enalaprilat and CPP-Ala-Ala-Phe-pAB, suggest that the kininase activity in the central nervous system of SHR is reduced in comparison to that of NWR. 5 The SHR also showed increased sensitivity to BK and Lys-Lys-BK, compared with the NWR, when the kinins were injected following the administration of a mixture of the kininase inhibitors, suggesting that mechanisms other than kininase activity may play a role in the increased sensitivity of the SHR to the central pressor action of kinins. 6 An in vivo characterization of the kinin receptors which mediate the central pressor response showed that the interaction with DAHTDBK was reversible and of competitive nature. The pA2 in vivo estimated for the kinin receptors of the SHR was 0.7 logarithm units larger than that obtained in the NWR. 7 The kinin receptors which mediate the central BK pressor effect in the SHR are of the BK2 subtype and are similar to receptors in the NWR. The increased sensitivity to kinins in the SHR may be explained, at least in part, by their decreased kininase activity. At present it is impossible to conclude whether the difference observed in the pA2 represents an increased affinity of the kinin receptors or can be attributed to differences amongst strains in the enzymatic degradation of the antagonist.

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Considering the intriguing relationship between immune system and behavior recently described in mammals, and the lack of information of this relationship in fish, here we describe for the first time the interaction between the immune system and social and exploratory behavior in zebrafish. Fish high responders to novelty (HRN) presented a proinflammatory profile, with increased IL-1β and reduced IL-10 expression compared to fish low responders to novelty (LRN). Likewise, fish less responsive to social stimuli have a reduced expression of INF-γ. We show that fish with different behavior patterns have differences in the immune response. Our findings indicate that the interplay between immune system and behavior in zebrafish is similar to that found in mammalian models and that zebrafish should be considered as a potential model organism to study the relationship between immune system and behavior.

The intracerebroventricular injection of bradykinin produces an increase in arterial blood pressure. The site of action for this effect has been reported to be in the lateral septal area, in the hypothalamus, or in the ventral portion of the third ventricle. Bradykinin injected into the fourth cerebral ventricle of unanesthetized rats produced a pressor effect with a shorter latency and a larger maximal effect than when injected in the third or lateral ventricles. Bradykinin in the fourth ventricle was also 10 times more potent than in the third ventricle and 100 times more potent than in the lateral ventricle. No changes in blood pressure were observed when bradykinin was injected into the cerebellum or in the subarachnoid space of the ventral surface of the brain or of the medulla. Microinjections in the medulla oblongata showed that the pressor responses were obtained when bradykinin was injected in the nucleus tractus solitarius or in the dorsal spinal trigeminal tract. No effect was observed after injections were given into the ventral, ventral lateral medulla, or other medullary regions. The data suggest that bradykinin may play a regulatory role in the central control of blood pressure by stimulating sites that are near the dorsal and dorsal lateral surfaces of the medulla and accessible to kinins in cerebrospinal fluid and in the cerebral arterial circulation.

Here we show that the feeding regimen modulates zebrafish (Danio rerio) behavior. With regard to the time elapsed between feeding and behavioral evaluation, fish fed 3 h before behavioral evaluation in the novel tank test (NTT) showed decreased activity and a trend toward an anxiolytic reaction (increased use of the upper section of the aquarium) in comparison to fish fed 0.5, 6, 12, 24 or 48 h before testing, although differences were not statistically significant for all comparisons. Activity and use of the upper section of the aquarium did not differ significantly among the other treatments. Regarding feeding frequency, fish fed once a day showed higher anxiety-like behavior (decreased use of the upper section of the aquarium) in comparison to fish fed twice a day, but feeding four or six times per day or only every second day did not result in differences from feeding twice a day. Feeding frequency had no effect on activity level. Metabolically, fish fed once a day presented decreased levels of glucose and glycogen and increased lactate when compared to the regular feeding (fish fed twice a day), suggesting that feeding regimen may modulate carbohydrate metabolism. Mechanistically, we suggest that the metabolic changes caused by the feeding regimen may induce behavioral changes. Our results suggest that the high variability of the results among different laboratories might be related to different feeding protocols. Therefore, if issues pertaining to the feeding regimen are not considered during experiments with zebrafish, erroneous interpretations of datasets may occur.