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

Investigamos nesse estudo o papel dos receptores 5-HT2C e da transmissão serotonérgica no controle do comportamento alimentar em codornas. Em grupo de aves em jejum, a administração do liberador de serotonina, fenfluramina (FEN) e dos agonistas 5-HT2C, mCPP e MK212, nas doses de 1,0 e 3,3 mg/Kg induziu a uma redução significativa da ingestão alimentar (0,71 ± 0,18 g e 0,47 ± 0,2 g; 0,49 ± 0,22 g e 0,48 ± 0,29 g; 0,82 ± 0,13 g e 0,71 ± 0,16 g; respectivamente). A ingestão de alimento nos grupos controles variou de 2,89 ± 0,21 g a 2,97 ± 0,22 g, 60 min após a reapresentação de alimento, P < 0,0001). Resultados similares foram obtidos com as codornas normoalimentadas. Tanto o liberador de serotonina, FEN, quanto os agonistas 5-HT2C, mCPP e MK212 em doses de 3,3 mg/Kg induziram resposta hipofágica (FEN, 0,78 ± 0,08 g; mCPP, 0,89 ± 0,07 g; MK212, 1,25 ± 0,17 g vs. controles, 2,05 ± 0,12 g, 120 min após a oferta de alimento, P < 0.0001 a P < 0.01). A administração prévia do antagonista 5-HT2C, LY53857 (5,0 mg/Kg) bloqueou a resposta hipofágica induzida pelos agonistas 5-HT2C, 60 min após a apresentação de alimento. Os resultados obtidos demonstram o papel modulatório da liberação de serotonina e dos receptores pós-sinápticos 5-HT2C, no controle do comportamento alimentar de codornas.

Effects of sumpathomimetic anorexigenic agent [fenfluramine] on some hepatic, haematological and thyroid functions in rabbits

Fenfluramine is a sympathomimetic-anorexigenic amphetamine derivative. Fentluramine may affect variable body systems during continuous use. No data as regard the influence of fenfluramine on ferrokinetics and hence this necessitates a proper line of investigation. This study was performed on 40 male Rabbits, divided into two groups; group I for studying liver functions,% saturation of transferrin, and some haematological parameters, group II for studying thyroid functions and radio-active 58Fe ferrokinetics. The results had shown that: 1. The chemical had led to significant decrease in liver functions and in serum iron. 2. No significant change was shown in the haematological parameters. 3. There was significant decrease in radio-iron in the plasma. 4. There was significant increase in T3 and T4. Thus the drug might have a deleterious effect on ferrokinetics, liver cells and thyroid gland therefore, it should be used cautiously

D-Fenfluramine selectively releases 5-HT from dorsal raphe terminals

The aim of this study was to investigate whether D-fenfluramine (FEN) releases 5-hydroxytryptamine (5-HT) selectively from dorsal raphe (DR) terminais. Male Wistar rats, 180-200 g, were implanted with microdialysis probes in the amygdala (Am; N = 5) and dorsal hippocampus (DH; N = 6) and 5-HT levels were measured by electrochemical detection. Under basal conditions, 5-HT levels were approximately 50 and 230 fmol per 30 min sample, in the Am and DH, respectively. FEN (1O mg/kg, ip) produced a 3-4-fold increase in 5HT relesse in the Am, but not in the DH. Since the Am is mainly innervated by DR fibers while the DH receives 5-HT input chiefly from the median raphe (MR), the present results support the view that FEN selectively releases 5-HT from DR terminals.

Effect of d-fenfluramine on cortical spreading depression in rats

We investigated the effect of a single ip injection of ed-fenfluramine (d-fen; 5-10 mg/kg), a serotinin reuptake blocker, on cortical spreading depression (SD) in 17 male Wistar rats (300-360 g body weight). SD was elicited at the right frontal cortex by 1-min application of 2 percent KCl at 20-min intervals. SD propagation was monitored (electrocorticogram and DC-recording) at 2 points on the right parietal surface for 3 h. After a "baseline" recording period (1 h), d-fen was injected and the recording session was continued for 2 h. When compared to the predrug SD velocities (t = 0 min) the values measured after d-fen decreased significantly at t = 20 min (3.44 + or - 0.63 vs 2.66 + or - 0.51 mm/min; N = 17, P<0.001), at t = 40 min (3.32 + or - 0.58 vs 2.53 + or - 0.52 mm/min; N = 14, P<0.001), att=60 min (3.68 + or - 0.63 vs 2.92 + or - 0.72 mm/min; N = 11, P<0.001) and at t = 80 min (3.57 + or - 0.61 vs 3.03 + or - 0.83 mm/min; N = 12, P<0.05) but not at t = 100 min (3.47 + or - 0.72 vs 3.31 + or - 0.88 mm/min; N = 12) nor at t = 120 min (3.44 + or - 0.67 vs 3.37 + or - 0.76 mm/min; N = 11). Furthermore, in 19 of 48 KCl stimulations (40 percent) performed ...

D-fenfluramine reduces anxiety induced by simulated public speaking

To further explore the role of serotonin (5-HT) in anxiety, 28 healthy volunteers received in a double-blind study d-fenfluramine (30 mg, p.o.) or placebo, and were submitted to a simulated public speaking test (SPS), consisting of speaking in front of a video camera. The SPS induced significant increases in subjective anxiety evaluated by the visual analogue mood scale of Norris [MANCOVA, F(1.66,39.93) = 8.51, P < 0.001], as well as in systolic blood pressure [F(3,72) = 5.70, P = 0.001] and in heart rate [F(3,72) = 3.95, P = 0.012]. The drug decreased the anxiety factor [F(1,23) = 5.21, P = 0.032], without significantly affecting physical sedation, mental sedation or other feelings and attitudes. Also, the physiological measurements were not significantly changed by d-fenfluramine. Reported evidence shows that d-fenfluramine releases 5-HT from nerve endings and blocks 5-HT reuptake, indirectly stimulating postsynaptic 5-HT receptors. Therefore, the present results indicate that 5-HT inhibits the neural substrate of SPS-induced anxiety

Changes in biochemical parameters of carbohydrate metabolism following fenfluramine administration in rats

Fenfluramine, an anorexigenic agent, is widely used in the treatment of obesity. Besides its anorectic effect, it may also have some effects on general metabolism with the consequence of weight loss. In this study, the effect of fenfluramine on the concentrations of some parameters related to carbohydrate metabolism was investigated. It was shown that the serum insulin level was reduced by 41%, four hours after fenfluramine administration, which was accompanied by the elevation of serum glucose levels by 26%. The liver glycogen content showed a transient reduction, but reached the control level four hours post-treatment. Corticosterone levels were elevated immediately, followed by a 20% reduction after four hours. The short-term effects of fenfluramine on thyroid hormones were not statistically significant. Administration of fenfluramine for two weeks did not change the glycogen content of the liver significantly, but 64% and 103% increases were observed after four and six weeks of drug treatment, respectively. Insulin levels showed a gradual increase so that by the end of six weeks, 153% increase in insulin level was observed. No significant changes in serum glucose levels were seen during the period of treatment. Corticosterone concentration remained unchanged up to four weeks of treatment but a 32% reduction was seen after six weeks. The levels of T [4] and T [3] showed a transient increase, followed by a significant decrease after six weeks of treatment. It is concluded that fenfluramine has some important metabolic effect that is related to its action in decreasing food intake and weight loss

Antagonism of apomorphine-induced cage climbing behaviour and methamphetamine stereotypy by fenfluramine in mice.

Pretreatment with fenfluramine (5 and 10 mg/kg, ip) in doses which induced head twitches was found to antagonize apomorphine-induced cage climbing behaviour and methamphetamine stereotypy in mice. Since fenfluramine (5 and 10 mg/kg) did not induce catalepsy it indicates that fenfluramine lacks postsynaptic striatal and mesolimbic dopamine receptor blocking activity and it is possible that the fenfluramine-induced enhancement of central 5-hydroxytryptamine neuronal transmission may be responsible for its antagonistic effect on apomorphine-induced climbing behaviour and methamphetamine stereotypy.