Die Bedeutung von Stickstoffmonoxid bei der Vermittlung der Urocortin-induzierten anorektischen und angstähnlichen Effekte bei der Ratte
Zusammenfassung der Projektergebnisse
Urocortin1 (Ucn1), a neuropeptide of the corticotrophin releasing factor family, has been reported to produce anxiogenic-like and long-lasting anorectic effects after administration into the ventricular system. Presence of both mRNA coding for Ucn1 and the mature neuropeptide in the hypothalamic supraoptic nucleus (SON) lead to the hypothesis that endogenous Ucn1 released within this brain area might be involved in food intake and behaviour. As a first step to test this hypothesis, we mimicked an increased extracellular Ucn1 concentration by administration of different doses of synthetic Ucn1 (0.001 to 1.0 µg) bilaterally into the SON of Wistar rats and monitored the behavioural consequences. General behavioural parameters and locomotor activity were assessed in the open field paradigm. Feeding behaviour was measured by analysing both food and water consumption in 24 hrs food deprived rats. Furthermore, a conditioned taste aversion study was performed to test for possible non-specific appetite-suppressing effects of the Ucn1 treatment. Ucn1 administration into SON of rat produced an inverted U-shaped dose response on behaviour and doses higher than 0.01 µg were unable to reproduce the effects of lower doses. Pre-treatment with CRFaR antagonist, Ast (0.1 µg), normalized the Ucn1 induced effects. In food intake studies, administration of high doses of synthetic Ucn1 induced pharmacological effects that are unlikely to be observed under physiological conditions. However in a parallel study where we compared the number of Ucn1 immunoreactive neurons between pregnant and virgin cycling rats in the npEW, we found that there is a decreased number of Ucn1 immunoreactive neurons in the npEW during late pregnancy in rats. This decrease in urocortinergic inputs to brain areas controlling feeding behavior might contribute to the altered feeding behavior and energy homeostasis observed during pregnancy. These results suggest endogenous Ucn1 to be involved in the control of the animals arousal and appetite state which is dependant on the amount of the neuropeptide available to the receptor.
Projektbezogene Publikationen (Auswahl)
- A. Fatima, M.F. Haroon, G. Wolf, M. Engelmann and M.G. Spina. Reduced urocortin 1 immunoreactivity in the non-preganglionic Edinger- Westphal nucleus during late pregnancy in rats. Regul Pept. 2007;143: 34-38
- Fatima A , Wolf G., Engelmann M. & Spina M. G. Urocortinl administered into the hypothalamic supraoptic nucleus affects open-field behaviour in rats.(VIIth World Congress on Neurohypophysial Hormones, Regensburg, Germany 2007)
- Fatima A, Wolf G, Spina M G, Makara, G L, Zelena D, Engelmann M. IncreasedPMID: 17391780 number of oxytocin and neuronal nitric oxide synthase containing cells in the supraoptic nucleus of arginine vasopressin deficient Brattleboro rats. "2nd Joint French-German NO-Meeting", Hamburg, Germany, October 5-7, 2006
- Fatima A, Wolf G., Engelmann M. & Spina M. G. Dose-dependent effects of urocortin administered into the hypothalamic supraoptic nucleus on feeding and motor behaviour in rats. FENS Forum 2006, Vienna, Austria (July 08- July 12, 2006). (Siehe online unter: http://fens2006.neurosciences.asso.fr/abstracts/R2/A043_7.html )
