Roles of 5-HT receptors in the release and action of secretin on pancreatic secretion in rats

5-Hydroxytryptamine (serotonin, 5-HT) is a hormone and neurotransmitter regulating gastrointestinal functions. 5-HT receptors are widely distributed in gastrointestinal mucosa and the enteric nervous system. Duodenal acidification stimulates not only the release of both 5-HT and secretin but also pancreatic exocrine secretion. We investigated the effect of 5-HT receptor antagonists on the release of secretin and pancreatic secretion of water and bicarbonate induced by duodenal acidification in anesthetized rats. Both the 5-HT(2) receptor antagonist ketanserin and the 5-HT(3) receptor antagonist ondansetron at 1-100 microg/kg dose-dependently inhibited acid-induced increases in plasma secretin concentration and pancreatic exocrine secretion. Neither the 5-HT(1) receptor antagonists pindolol and 5-HTP-DP nor the 5-HT(4) receptor antagonist SDZ-205,557 affected acid-evoked release of secretin or pancreatic secretion. None of the 5-HT receptor antagonists affected basal pancreatic secretion or plasma secretin concentration. Ketanserin or ondansetron at 10 microg/kg or a combination of both suppressed the pancreatic secretion in response to intravenous secretin at 2.5 and 5 pmol x kg(-1) x h(-1) by 55-75%, but not at 10 pmol x kg(-1) x h(-1). Atropine (50 microg/kg) significantly attenuated the inhibitory effect of ketanserin on pancreatic secretion but not on the release of secretin. These observations suggest that 5-HT(2) and 5-HT(3) receptors mediate duodenal acidification-induced release of secretin and pancreatic secretion of fluid and bicarbonate. Also, regulation of pancreatic exocrine secretion through 5-HT(2) receptors may involve a cholinergic pathway in the rat.     

Study of GABA<Subscript>A</Subscript> receptors on the sleep-like behavior in <Emphasis Type="Italic">Coturnix japonica</Emphasis> (Temminck Schlegel, 1849) (Galliformes: Aves)

The present study was carried out to investigate the influence of GABA_A signaling on sleep-like behaviors through systemic administration of bicuculline and picrotoxin (GABA_A antagonists) and thiopental (an allosterical modulator). A thiopental (20 mg/kg) injection increased the eye closure frequency compared to the control group. The birds quickly became sleepy with a low frequency of early behavioral stages, such as rapid oral movement (ROM), feather ruffling and blinking. A bicuculline administration (1 and 4 mg/kg) did not modify the frequency of feather ruffling, ROM, eye closure or blinking responses. A lower dose of picrotoxin (2 mg/kg) stimulated an active awakening status, while an intermediate dose (4 mg/kg) elicited a moderate awakening status, which was associated with an increase in the frequency of ROM, blinking and eye closure. At the higher dose (8 mg/kg), the birds exhibited thermoregulatory-like behaviors and convulsions immediately after the injection. Interestingly, picrotoxin (4 mg/kg) intensified the eye closures when given in combination with thiopental (20 mg/kg). Both barbiturate and picrotoxin-induced sleep-like responses have the same behavioral neuropharmacological properties, conceivably because they are correlated with action at an identical site on the GABA_A receptor.     

Evidence indicating participation of the serotonergic system in controlling feeding behavior in Coturnix japonica (Galliformes: Aves).

We investigated participation of the brain serotonergic system in food intake control by using oral and systemic administration of serotonin precursors in quails (Coturnix japonica). Dietary supplemental tryptophan (0.1-50.0 g/kg) provoked a dose-dependent inhibition of food intake during a 5-h observation period, which persisted up to 24 h for doses of 30.0 and 50.0 g/kg. Normally fed and fasted animals treated with hydroxytryptophan (12.5-50.0 mg/kg) by the intracoelomic route showed an acute inhibition of food intake. Hypophagia in fasted birds was only effective when the precursor was administered immediately before food presentation. A similar response was obtained by administering serotonin (0.125-2.5 mg/kg, sc), with animals showing a hypnogenic response within the first ten minutes after administration, suggesting that, in contrast to mammals, the amine crosses the blood-brain barrier in quails. Administration of hydroxytryptophan at all doses tested induced significant dipsogenic behavior despite the concomitant hypnogenic response. The results suggest the involvement of serotonergic pathways in food intake control in quails and also show, for the first time, hypnogenic action induced by serotonin and a hyperdipsic effect elicited by hydroxytryptophan.     

Serotonin receptor subtypes required for ventilatory long-term facilitation and its enhancement after chronic intermittent hypoxia in awake rats

Respiratory long-term facilitation (LTF), a serotonin-dependent, persistent augmentation of respiratory activity after episodic hypoxia, is enhanced by pretreatment of chronic intermittent hypoxia (CIH; 5 min 11-12% O2-5 min air, 12 h/night for 7 nights). The present study examined the effects of methysergide (serotonin 5-HT1,2,5,6,7 receptor antagonist), ketanserin (5-HT2 antagonist), or clozapine (5-HT2,6,7 antagonist) on both ventilatory LTF and the CIH effect on ventilatory LTF in conscious male adult rats to determine which specific receptor subtype(s) is involved. In untreated rats (i.e., animals not exposed to CIH), LTF, induced by five episodes of 5-min poikilocapnic hypoxia (10% O2) separated by 5-min normoxic intervals, was measured twice by plethysmography. Thus the measurement was conducted 1-2 days before (as control) and approximately 1 h after systemic injection of methysergide (1 mg/kg ip), ketanserin (1 mg/kg), or clozapine (1.5 mg/kg). Resting ventilation, metabolic rate, and hypoxic ventilatory response (HVR) were unchanged, but LTF ( approximately 18% above baseline) was eliminated by each drug. In CIH-treated rats, LTF was also measured twice, before and approximately 8 h after CIH. Vehicle, methysergide, ketanserin, or clozapine was injected approximately 1 h before the second measurement. Neither resting ventilation nor metabolic rate was changed after CIH and/or any drug. HVR was unchanged after methysergide and ketanserin but reduced in four of seven clozapine rats. The CIH-enhanced LTF ( approximately 28%) was abolished by methysergide and clozapine but only attenuated by ketanserin (to approximately 10%). Collectively, these data suggest that ventilatory LTF requires 5-HT2 receptors and that the CIH effect on LTF requires non-5-HT2 serotonin receptors, probably 5-HT6 and/or 5-HT7 subtype(s).     

Serum and serotonin induce retraction of calf aortic smooth muscle (CASM) cells in vitro: inhibition by ketanserin, a 5-HT2 receptor antagonist

Calf aortic smooth muscle (CASM) cells cultured in vitro at high cell density (4 x 10(4) cells/cm2) on bacteriological petri dishes in the presence of serum pile up in clusters and create open spaces in the monolayer. This phenomenon is clearly visible 6 days after plating and is markedly enhanced by the addition of fetal calf serum. Serotonin is essential for the serum-induced retraction since (1) dialyzed serum has no effect, (2) of all the vasoactive agents we tested, only serotonin induced a similar degree of retraction, and (3) the serum-induced retraction was completely blocked by preincubating the cells with serotonin 5-HT2 receptor blockers such as ketanserin and ritanserin but not by preincubation with adrenergic-alpha 1 blockers or histamine antagonists. Serotonin caused CASM cell retraction in a dose-dependent way, with a maximum effect at 10(-6) M. The serotonin-induced retraction was reversible in time and was effectively blocked by ketanserin (IC50 = 1.2 x 10(-9) M). It is therefore concluded that serotonin induces retraction of CASM cells, mediated by the serotonin 5-HT2 receptor.     

Serotonin-induced hypoglycemia and increased serum insulin levels in mice

The effects of serotonin (5-HT) on plasma glucose levels were studied. 5-HT above 20 mg/kg induced apparent hypoglycemia in mice. The hypoglycemic effects of 5-HT were strongly antagonized by methysergide but only partially inhibited by ketanserin. However, ICS 205-930 was without effect. This indicates that the hypoglycemia induced by 5-HT is mediated by both the 5-HT1 and 5-HT2 receptors. 5-HT also produced an increase in serum immunoreactive insulin (IRI) which was completely inhibited by methysergide and partially antagonized by ketanserin. It is suggested that the 5-HT-induced increase in IRI is elicited by the activation of the 5-HT1 and 5-HT2 receptors, which is similar to the results obtained with plasma glucose. These results indicate that the 5-HT receptors may regulate blood glucose levels by modifying the release of insulin.     

Influence of serotonergic transmission anD postsynaptic 5-HT2C action on the feeding behavior of Coturnix japonica (Galliformes: Aves).

We investigated the role of 5-HT2C receptors and serotonergic transmission in the feeding behavior control of quails. Administration of serotonin releaser, fenfluramine (FEN) and 5-HT2C agonists, mCPP and MK212, 1.0 and 3.3 mg/Kg induced significant inhibition of food intake in previously fasted fowls (0.71 +/- 0.18 g and 0.47 +/- 0.2 g; 0.49 +/- 0.22 g and 0.48 +/- 0.29 g; 0.82 +/- 0.13 g and 0.71 +/- 0.16 g, respectively). Control groups ranged from 2.89 +/- 0.21 g to 2.97 +/- 0.22 g, 60 min after reintroduction of food, P < 0.0001). Similar results were obtained with normally fed quails. Both serotonin releaser and 5-HT2C agonists, in a 3.3 mg/Kg dose, induced hypophagy (FEN, 0.78 +/- 0.08 g; mCPP, 0.89 +/- 0.07 g; MK212, 1.25 +/- 0.17 g vs. controls, 2.05 +/- 0.12 g, 120 min after food was presented, P < 0.0001 to P < 0.01). Previous administration of 5-HT2C antagonist, LY53857 (5.0 mg/Kg) blocked the hypophagic response induced by 5-HT2C agonists 60 min after food was reintroduced. Current data show a modulatory role of serotonin release and postsynaptic 5-HT2C receptors in the feeding behavior of quails.     

Influence of 5-HT1A agonist on the feeding behavior of Coturnix japonica (Galliformes: Aves).

In this study, we investigate the effect of serotonin receptor 5-HT1A stimulation on the feeding behavior of quails (Coturnix japonica). The administration of 5-HT1A agonist, 8-OH-DPAT (0.05 to 5.0 mg/Kg) dose-dependently inhibited the food intake in normally fed quails. Greater inhibition was attained with 5.0 mg/kg (0.93 +/- 0.21 g vs. 5.83 +/- 0.25 g, P < 0.05, 2 h after food offer). A comparable response was obtained from previously fasted quails. At end of 2 h, a higher dose of 8-OH-DPAT induced more intense hypophagy (1.59 +/- 0.41 g vs. 6.85 +/- 1.04 g, P < 0.0001). Previous treatment with the antagonist 5-HT1A/beta-adrenergic, propranolol, failed to block the inhibitory action of 8-OH-DPAT, but instead, intensified it (controls, 5.22 +/- 1.09 g; 8-OH-DPAT, 1.41 +/- 0.19 g; propranolol + 8-OH-DPAT, 0.44 +/- 0.25 g, P < 0.01, for all comparisons). The administration of an isolated higher dose of propranolol induced a hypophagic action (controls, 4.5 +/- 0.8 g vs. propranolol, 2.0 +/- 0.2 g, P < 0.01). Current outcomes suggest a possible role of 5-HT1A receptor on the feeding behavior of quails, as opposed to mammals. On the other hand, the intensified hypophagy induced by previous administration of propranolol raises the hypothesis of a beta-adrenergic excitatory mechanism that controls the feeding behavior of quails.     

5-Hydroxytryptamine initiates pulsatile urea excretion from perfused gills of the gulf toadfish (Opsanus beta)

When stressed, toadfish become ureotelic and excrete almost all of their nitrogenous waste in 1-3 daily pulses of urea-N across the gills. Intravascular injections of 5-hydroxytyptamine (5-HT; serotonin) and analogues also elicit marked excretory pulses of urea-N from toadfish in vivo, suggesting that 5-HT release is the proximate trigger for spontaneous pulses. However it is unclear whether 5-HT is acting on the gills directly or elsewhere to cause the effect indirectly. A perfused whole gill preparation which maintained normal pressure relationships and stable vascular resistance was employed to address this question. Bolus injections into the ventral aortic perfusate of either 5-HT (1, 10 μmol kg(-1)) or the specific 5-HT(2) receptor agonist α-methyl 5-HT (1, 10 μmol kg(-1)) elicited rapid urea-N pulses from perfused toadfish gills. The effective doses, the post-injection delays (5.5 ± 1.3 min, range=2-22), the percent occurrences (57-85%), and the magnitude of the induced urea-N pulses (615.4 ± 131.3 μmol-N kg(-1), range 66.0-2634.0), were all similar to those previously reported when these agents were injected in vivo. Bolus injections of 5-HT and α-methyl 5-HT also elicited a biphasic response in ventral aortic pressure, reflecting an initial rapid short-lived vasodilation and a subsequent longer-lasting vasoconstriction. These events were similar to those which have been recorded to occur at a greater frequency during spontaneous urea-N pulsing in vivo. Neither the urea-N pulsing nor the cardiovascular responses to 5-HT were inhibited by the 5-HT(2A) receptor subtype blocker, ketanserin (pre-injection with 10 μmol kg(-1) plus 33 μmol L(-1) in the perfusate). Overall, these results provide strong support for the idea that the proximate stimulus for natural urea pulsing in vivo is 5-HT mobilization, acting directly in the gills.     

On the role of serotonin2A/2C receptors in the sensitization to cocaine.

Apart from showing involvement of dopamine, recent studies also indicate a role of serotonin (5-HT) in the behavioral effects of cocaine in rodents. In the present study we investigated the role of 5-HT2A/2C receptors in the development or expression of sensitization to cocaine in rats, using ketanserin, an antagonist at these receptors. Since ketanserin also shows a high affinity for alpha1-adrenoceptors, prazosin, a comparative antagonist at those receptors was also examined. Male Wistar rats were treated repeatedly (for 5 days) with cocaine (10 mg/kg) in combination with either vehicle, or ketanserin (1-3 mg/kg) or prazosin (3 mg/kg); afterwards, on day 10, they received a challenge dose of cocaine (10 mg/kg). In another experiment, the animals were given either with vehicle or cocaine (10 mg/kg) for 5 days, and were then challenged with cocaine (10 mg/kg) in combination with vehicle, or ketanserin (1-3 mg/kg) or prazosin (3 mg/kg) on day 10. Acute administration of cocaine increased the locomotor activity in rats; that hyperactivation was inhibited by ketanserin (3 mg/kg), but not by prazosin. In animals treated repeatedly with cocaine, the locomotor hyperactivity induced by a challenge dose of the psychostimulant was ca. 2-3 times higher than that after its first administration. No difference was observed in the response to cocaine challenge in rats treated repeatedly with cocaine, ketanserin+cocaine, or prazosin+cocaine. In animals treated repeatedly with the psychostimulant, the behavioral response to a challenge dose of cocaine was dose-dependently decreased when the drug was combined with ketanserin, but not with prazosin. The above findings indicate a role of 5-HT2A/2C receptors (but not alpha1-adrenoceptors) in the acute locomotor hyperactivity, as well as in the expression (but not development) of cocaine sensitization. Since chronic use of cocaine by humans may lead to psychoses or craving for this drug of abuse, our findings also seem to indicate possible importance of 5-HT2A/2C receptor antagonists in the therapy of cocaine addiction.     

Intracerebroventricular serotonin reduces the degree of acute hypoxic ventilatory depression in peripherally chemodenervated rabbits

Hypoxia causes changes in the rate of synthesis or release of neurotransmitters in the brain. The accumulation of serotonin (5-HT) in the central nervous system might cause hypoxic respiratory depression. In the present study, we aimed to examine the role of central 5-HT on normoxic and acute hypoxic ventilatory depression (AHVD) in peripheral chemoreceptors denervated rabbits. All experiments were performed in peripherally chemodenervated rabbits anesthetized with intravenous injection of urethane (400 mg/kg) and alpha-chloralose (40 mg/kg). For intracerebroventricular (ICV) administration of 5-HT (20 microg/kg) and ketanserin (10 microg/kg), a cannula was placed in left lateral ventricle by stereotaxic method. Respiratory frequency (fR), tidal volume (VT), ventilation minute volume (VE) and systemic arterial bood pressure (BP) were recorded in each experimental phases and mean arterial pressure was calculated (MAP). Heart rate (HR) was also determined from the pulsation of BP. The effects of ICV serotonin and ICV ketanserin on the indicated parameters during air breathing (normoxia) and breathing of hypoxia (8% O2--92% N2) were investigated. During hypoxia, fR, VT, VE, MAP and HR decreased, and AHVD was thus obtained. ICV injection of 5-HT during normoxia caused significant increases in VT (P < 0.001) and in VE (P < 0.01). On the other hand, ICV 5-HT injection reduced the degree of AHVD in peripherally chemodenervated rabbits during hypoxia (fR; P < 0.05, VT; P < 0.05 and VE; P < 0.01). After ICV injection of ketanserin, the enhancement of 5-HT on VE was prevented during normoxia. On the breathing of hypoxic gas after ICV ketanserin, the degree of AHVD was augmented. In conclusion, our findings suggested that central 5-HT increases normoxic ventilation and reduces the degree of AHVD during hypoxia and that ICV ketanserin prevents the stimulatory effect of 5-HT on respiration and augments AHVD.     

Brain neurotransmitter receptor-binding characteristics in rats after oral administration of haloperidol, risperidone and olanzapine

The present study was conducted to characterize the binding of neurotransmitter receptors (dopamine D(2), serotonin 5-HT(2), histamine H(1), adrenaline alpha(1) and muscarine M(l) receptors) in the rat's brain after the oral administration of haloperidol, risperidone, and olanzapine. Haloperidol at 1 and 3 mg/kg displayed significant activity to bind the D(2) receptor (increase in the Kd value for [(3)H]raclopride binding) in the corpus striatum with little change in the activity toward the 5-HT(2) receptor (binding parameters for [(3)H]ketanserin). In contrast, risperidone (0.1-3 mg/kg) showed roughly 30 times more affinity for the 5-HT(2) receptor than D(2) receptor. Also, olanzapine (1-10 mg/kg) was most active toward the H(1) receptor in the cerebral cortex, corpus striatum, and hippocampus, was less active in binding 5-HT(2) and D(2) receptors, and showed the least affinity for alpha(1) and M(1) receptors. In conclusion, haloperidol and risperidone administered orally selectively bind D(2) and 5-HT(2) receptors, respectively, in the rat brain, while olanzapine binds H(1), 5-HT(2), and D(2) receptors more than alpha(1) and M(1) receptors.     

Effects of ketanserin on DOI-, MCPP- and TRH-induced prolactin secretion in estrogen-treated rats.

The effects of ketanserin (Ket), a serotonin (5-HT2) receptor antagonist, on DOI- and mCPP-, two 5-HT agonists, and TRH-induced PRL secretion were studied. Adult female Sprague-Dawley rats ovariectomized for two weeks and treated with a long-acting estrogen, polyestradiol phosphate for one week were used. Drug administration and serial blood sampling were accomplished through indwelling intraatrial catheters which were implanted two days before the experiment. Both DOI (0.5 mg/kg BW) and mCPP (1 mg/kg BW) stimulated prolactin secretion within 10 min after iv injection and the effects were diminished by 30 min. In animals pretreated with Ket (5 mg/kg BW, sc), the effect of DOI was blocked, while that of mCPP was augmented. Co-administration of Ket (1 mg/kg BW, iv) with DOI or mCPP produced similar effect. Pretreatment with Ket, similar to sulpiride (Sulp), a dopamine antagonist, potentiated the TRH-induced prolactin secretion. Co-administration of Ket and Sulp further potentiated the TRH action. It is concluded that Ket not only acts as a 5-HT2 receptor antagonist that blocks the action of DOI, but may also act on dopamine receptor(s) with lower sensitivity to Sulp.     

Ketanserin modulates rabbit foot cooling in the presence or absence of exogenous serotonin

Since hypothermic conditions augment sensitivity to vasoactive amines like serotonin (5-HT) and 5-HT is associated with the etiology of Raynaud's phenomenon, this amine perhaps plays a role in cold-induced vasoconstriction. To determine if 5-HT participated in normal peripheral cooling and if ketanserin (KET), a 5-HT blocker, modulated such cooling, four groups of New Zealand white rabbits (N = 33) were studied. The femoral artery was cannulated to allow perfusion of a hindlimb. Thermistors were implanted in the footpad and rectum. The hindfoot was exposed to a 15 degrees C bath for 30 min, while footpad and rectal temperatures were recorded. During cold exposure, 5-HT (5 x 10(-2) M, group 1), KET (0.1 mg/kg) + 5-HT (group 2), KET (group 3), or saline (group 4) was perfused through the hindlimb. Groups 2 and 3 were also pretreated with KET (0.1 mg/kg perfused over 30 min). The rabbit footpad cooled rapidly when exposed to exogenous 5-HT (group 1). KET treatment in the presence of exogenous 5-HT (group 2) was associated with a significantly (P less than 0.05) reduced cooling rate. KET treatment in the absence of exogenous 5-HT (group 3) was also associated with a significantly (P less than 0.05) elevated limb temperature when compared to controls (group 4). This suggested that endogenous 5-HT participated in limb cooling. Therefore, as noted for Raynaud's disease, 5-HT may also influence peripheral cooling of tissues free of such pathologies.(ABSTRACT TRUNCATED AT 250 WORDS)     

Functional expression of the serotonin transporter in immortalized rat brain microvessel endothelial cells

There is evidence from recent studies that the brain endothelium (of capillaries and/or larger vessels) may serve as a specific target for serotonin [5-hydroxytryptamine (5-HT)]. This neurotransmitter is expected to be involved in the regulation of the blood-brain barrier (BBB) permeability and/or of the cerebral blood flow via receptor-mediated mechanisms. Effective control of these processes depends on a speedy uptake and metabolism of released 5-HT molecules. To realize this, a similar mechanism of 5-HT uptake as in brain may exist at the BBB. In this study, we have demonstrated using RT-PCR that 5-HT transporter mRNA is present in the brain endothelium and that a saturable transport system for 5-HT is functionally expressed in immortalized rat brain endothelial cells (RBE4 cells). These cells take up [3H]5-HT by an active saturable process with a Km value of 397 +/- 64 nmol/L and a transport capacity of 51.7 +/- 3.5 pmol x g(-1) x min(-1). The 5-HT uptake depends on Na+, as indicated by the replacement of NaCl by LiCl. The 5-HT uptake was sensitive to specific 5-HT transport inhibitors such as paroxetine, clomipramine, fluoxetine, and citalopram but not to inhibitors of the vesicular amine transporter such as reserpine or tetrabenazine. Our results demonstrate that cerebral endothelial cells are able to participate actively in the removal and metabolism of the released 5-HT, which supports the concept of direct serotoninergic regulation of the BBB function.     

Effects of the S2-serotonergic receptor antagonist, ketanserin, on cerulein-induced pancreatitis in the rat.

We investigated the effects of ketanserin, a S 2 (5-hydroxytryptamine 2; 5-HT 2)-serotonergic receptor antagonist, on cerulein-induced pancreatitis in the rat. Large pharmacological doses of cerulein induced acute pancreatitis in the rat. Ketanserin reduced the cerulein-induced increase in serum amylase concentration in a dose-dependent manner. Treatment with 10 mg/kg of ketanserin per os markedly improved cerulein-induced pancreatitis and was associated with a significant reduction of the increase in serum amylase concentration. In addition, a very specific serotonin S 2 antagonist, ritanserin which has no antihypertensive effect, also reduced the cerulein-induced increase in the serum amylase concentration. These results suggest that S 2 (5-HT 2) may play a role in pathophysiology of cerulein-induced pancreatitis in the rat.     

Serotoninergic control of somatostatin and gastrin release from the isolated rat stomach

The influence of exogenous serotonin on the secretion of gastric somatostatin and gastrin was investigated under in vitro conditions using an isolated, vascularly perfused rat stomach preparation. Serotonin stimulated gastrin release, maximal effects were observed at 10(-6) M which increased gastrin levels by 78%; on the contrary, somatostatin secretion was inhibited (maximal inhibition of 56% at 10(-6) M). Changes in hormone secretion in response to serotonin were reversed by combined blockade of 5-HT1 and 5-HT2 receptors by methysergide and blockade of 5-HT2 receptors by ketanserin (10(-5) and 10(-6) M, respectively), and of cholinoreceptors by atropine (10(-5) M). It is concluded that in rats in vitro serotonin inhibits release of gastric somatostatin and stimulates gastrin secretion via specific serotonin receptors but muscarinic cholinergic receptors are also involved.     

Serotonin inhibition of tumor necrosis factor-alpha synthesis by human monocytes

Serotonin inhibited in a concentration dependent way (10(-3) M to 10(-10) M) the LPS induced Tumor Necrosis Factor-alpha synthesis both, when added to the monocyte cultures from the beginning and when added together with the activating stimulus 8 hours before the end of the culture. The inhibitory effect was specifically blocked by the 5-HT1 and 5-HT2 serotonin antagonist methysergide and the 5-HT2 receptor antagonist ketanserin. This indicates that only the 5-HT2 receptor family (5-HT2 or 5-HT1C) may be involved in the inhibitory effect. Serotonin seems to play an important immunomodulatory role in macrophage functions.     

Effect of L-5-Hydroxytryptophan on drinking behavior in Coturnix japonica (Temminck and Schlegel, 1849) (Galliformes: Aves): involvement of renin-angiotensin system

The purpose of this study was to explore the role of L-5-hydroxytryptophan (L-HTP) and its relationship with the renin-angiotensin system (RAS) on the drinking behavior in Japanese quails. Normally-hydrated quails that received injections of L-HTP (12.5; 25 and 50 mg.kg-1) by the intracoelomic route (ic) expressed an increase in water intake, which was inhibited by captopril, an angiotensin converting enzyme (ACE) inhibitor. In addition, captopril also induced such a response in birds under previous fluid deprivation. High doses of captopril (35-70 mg.kg-1, sc) in normally-hydrated quails decreased the spontaneous water intake while low doses of captopril (2-5 mg.kg-1, sc) did not prompt water intake after L-HTP administration. Losartan, an AT1 receptor antagonist in mammals, did not change the water intake levels in normally-hydrated or water-deprivated birds. Serotonin (5-HT) injections did not provoke its known dipsogenic response.     

Serotonin regulates rhythmic whisking

Many rodents explore their environment by rhythmically palpating objects with their mystacial whiskers. These rhythmic whisker movements ("whisking"; 5-9 Hz) are thought to be regulated by an unknown brainstem central pattern generator (CPG). We tested the hypothesis that serotonin (5-HT) inputs to whisking facial motoneurons (wFMNs) are part of this CPG. In response to exogenous serotonin, wFMNs recorded in vitro fire rhythmically at whisking frequencies, and selective 5-HT2 or 5-HT3 receptor antagonists suppress this rhythmic firing. In vivo, stimulation of brainstem serotonergic raphe nuclei evokes whisker movements. Unilateral infusion of selective 5-HT2 or 5-HT3 receptor antagonists suppresses ipsilateral whisking and substantially alters the frequencies and symmetry of whisker movements. These findings suggest that serotonin is both necessary and sufficient to generate rhythmic whisker movements and that serotonergic premotoneurons are part of a whisking CPG.