J.J. Pérez-Maceira

Hypothalamic neuropeptide Y (NPY) gene expression is not affected by central serotonin in the rainbow trout (Oncorhynchus mykiss).

Mammalian studies have shown a link between serotonin (5-HT) and neuropeptide Y (NPY) in the acute regulation of feeding and energy homeostasis. Taking into account that the actions of 5-HT and NPY on food intake in fish are similar to those observed in mammals, the objective of this study was to characterize a possible short-term interaction between hypothalamic 5-HT and NPY, by examining whether 5-HT regulates NPY gene expression, to help clarify the mechanism underlying the observed anorexigenic action of central 5-HT in the rainbow trout. We used qRT-PCR to determine the levels of NPY mRNA in the hypothalamus-preoptic area (HPA) of rainbow trout after intraperitoneal (i.p.) injection of a single dose of dexfenfluramine (dFF, 3mgkg(-1); 24h-fasted and fed fish) or intracerebroventricular (i.c.v.) administration of 5-HT (100μgkg(-1); 24h-fasted fish). Significant suppression of food intake was observed after administration of 5-HT and dFF. No significant changes in NPY gene expression were obtained 150min after administration of 5-HT or dFF. However, administration of the 5HT1B receptor agonist anpirtoline did not have any significant effect on food intake in rainbow trout. The results suggest that in fish, unlike in mammals, neither the NPY neurons of the HPA nor the 5-HT1B receptor subtype participate in the neural circuitry involved in the inhibition of food intake induced by central serotoninergic activation.

Serotonin-induced brain glycogenolysis in rainbow trout (Oncorhynchus mykiss)

SUMMARY In this study, we evaluated the serotonin-mediated control of cerebral glycogen levels in the rainbow trout, Oncorhynchus mykiss. Intracerebroventricular (i.c.v.) administration of serotonin (5-HT) to normoglycemic trout (time and dose response) decreased glycogen levels in the brain and increased brain glycogen phosphorylase activity (time response). In hypoglycemic fish (that had been fasted for 5 and 10 days), there was a time-dependent decrease in brain glycogen levels; under these conditions, i.c.v. administration of 5-HT also reduced the brain glycogen content in fish that had been fasted for 5 days. In fish with local cerebral hypoglycemia (induced by 2-DG administration), the glycogen levels decreased and, as above, i.c.v. administration of 5-HT also lowered the glycogen content. In hyperglycemic fish, 5-HT did not affect glycogen levels. Administration of receptor agonists 5-HT1A (8-OH-DPAT), 5-HT1B (anpirtoline and CP93129) or 5-HT2 (α-m-5-HT) decreased the brain glycogen levels. This effect was antagonized by the administration of receptor antagonists 5-HT1A (WAY100135 and NAN190), 5-HT1B (NAS181) and 5-HT2B/C (SB206553). Administration of the receptor agonists (±)-DOI (5-HT2A/2C), m-CPP (5-HT2B/2C), BW723C86 (5-HT2B) and WAY 161503 (5-HT2C) led to decreases in the levels of brain glycogen. We found that 5-HT is involved in the modulation of brain glycogen homeostasis in the rainbow trout, causing a glycogenolytic effect when fish are in a normoglycemic or hypoglycemic state, but not when they are in a hyperglycemic state. 5-HT1A, 5-HT1B, 5HT2B and 5-HT2C-like receptors appeared to be involved in the glycogenolytic action of 5-HT, although the effect mediated by 5-HT1A or 5-HT1B was apparently stronger.

Homeostasis of glucose in the rainbow trout (Oncorhynchus mykiss Walbaum): the role of serotonin.

SUMMARY In this study, we evaluated, for the first time, the 5-HT (serotonin)-mediated control of glucose homeostasis in the rainbow trout Oncorhynchus mykiss. Intraperitoneal administration of 5-HT increased plasma levels of glucose, adrenaline and noradrenaline. By contrast, intracerebroventricular administration of 5-HT did not cause any significant variation in plasma levels of glucose. The release of endogenous 5-HT following intraperitoneal administration of d-fenfluramine led to a significant increase in plasma levels of glucose and adrenaline. Intraperitoneal administration of (1) MIAN (a 5-HT2 receptor antagonist) did not block either the hyperglycaemic action or the increase in plasma levels of adrenaline induced by 5-HT, but did block the increase in plasma levels of noradrenaline, and (2) 5-CT (a 5-HT1 agonist) increased the plasma levels of glucose and of adrenaline, without altering those of noradrenaline. Administration of TFMPP (a 5-HT1B agonist) did not increase the plasma levels of glucose, and the hyperglycaemic action of 5-HT was not blocked by antagonists of 5-HT1A (WAY 100635), 5-HT1D (BRL 15572), 5-HT2B (SB 204741) or 5-HT7 (pimozide) receptors. It was demonstrated that, in rainbow trout, peripheral 5-HT, but not brain 5-HT intervenes in the modulation of glucose homeostasis with a hyperglycaemic effect. This effect is associated with the release of adrenaline and activation of 5-HT1-like receptors. As far as could be determined in the present study, these 5-HT1-like receptors are unrelated to either the 5-HT1A, 5-HT1B or 5-HT1D receptor subtypes of mammals. The 5-HT2-type receptors may mediate the release of noradrenaline, but not of adrenaline, and furthermore, do not appear to play an important role in the hyperglycaemic effect exerted by 5-HT.

Brain glycogen supercompensation after different conditions of induced hypoglycemia and sustained swimming in rainbow trout (Oncorhynchus mykiss).

Brain glycogen is depleted when used as an emergency energy substrate. In mammals, brain glycogen levels rebound to higher than normal levels after a hypoglycemic episode and a few hours after refeeding or administration of glucose. This phenomenon is called glycogen supercompensation. However, this mechanism has not been investigated in lower vertebrates. The aim of this study was therefore to determine whether brain glycogen supercompensation occurs in the rainbow trout brain. For this purpose, short-term brain glucose and glycogen contents were determined in rainbow trout after being subjected to the following experimental conditions: i) a 5-day or 10-day fasting period and refeeding; ii) a single injection of insulin (4 mg kg(-1)) and refeeding; and iii) sustained swimming and injection of glucose (500 mg kg(-1)). Food deprivation during the fasting periods and insulin administration both induced a decrease in glucose and glycogen levels in the brain. However, only refeeding after 10 days of fasting significantly increased the brain glycogen content above control levels, in a clear short-term supercompensation response. Unlike in mammals, prolonged exercise did not alter brain glucose or glycogen levels. Furthermore, brain glycogen supercompensation was not observed after glucose administration in fish undergoing sustained swimming. To our knowledge, this is the first study providing direct experimental evidence for the existence of a short-term glycogen supercompensation response in a teleost brain, although the response was only detectable after prolonged fasting.