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C Bendotti

Publications and source records attributed to C Bendotti.

At least 73 records · Page 4Linked to original sources
PubMed1986

8-Hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) elicits eating in free-feeding rats by acting on central serotonin neurons.

A subcutaneous injection of 0.5 mg/kg 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), a drug with high affinity for 5-hydroxytryptamine (5-HT1A) binding sites, substantially increased eating in non-deprived rats. Intraventricular injections of 5,7-dihydroxytryptamine (5,7-DHT), a neurotoxin for 5-HT neurons, also significantly increased eating in rats and antagonized the effect of 8-OH-DPAT. Microinjections of 8-OH-DPAT (0.5 and 1 microgram) in the nuclei dorsalis and medianus raphe also significantly increased eating in rats. 8-OH-DPAT appears to stimulate eating by acting on 5-HT-containing neurons. These results are compatible with the hypothesis that a decrease in central 5-HT function disinhibits feeding.

5,7-Dihydroxytryptamine↗
PubMed1986

Further evidence of the inhibitory role of perifornical hypothalamic beta-adrenergic receptors in the feeding behaviour of hungry rats.

The reduction of food intake in hungry rats induced by salbutamol (10 mg/kg/i.p.) was prevented by IPS 339 (5 mg/kg, i.p.) a selective beta 2 adrenergic antagonist, but not by metoprolol (10 mg/kg i.p.), a blocker of beta 1 adrenergic receptors. Similarly, bilateral injections of IPS 339 (32 micrograms/1 microliter) but not metoprolol (80 micrograms/1 microliter) in the perifornical hypothalamic area completely antagonized the anorectic effect of intraperitoneal salbutamol, suggesting an involvement of beta 2 adrenergic receptors in this brain area. Clenbuterol, a beta 2 adrenergic agonist which readily crosses the blood-brain barrier, was 10-100 times more potent than salbutamol in inhibiting feeding consumption of deprived rats when injected intraperitoneally and this effect was also selectively antagonized by pretreatment with IPS 339. Neither IPS 339 nor metoprolol injected in the perifornical hypothalamus significantly modified the anorectic effect of diethylpropion (5 mg/kg i.p.) whereas it was partially prevented by intraperifornical injection of 1-propranolol (52 micrograms/2 microliter), a non-selective beta antagonist, suggesting that both beta 1 and beta 2 adrenergic receptors in the hypothalamus contribute to the mechanism by which diethylpropion causes anorexia.

Adrenergic beta-Agonists↗
PubMed1986

Selective involvement of dopamine in the nucleus accumbens in the feeding response elicited by muscimol injection in the nucleus raphe dorsalis of sated rats.

Muscimol injection (100 ng) in the nucleus raphe dorsalis (NRD) caused intense eating in non-food-deprived rats. At a dose (10 micrograms) blocking dopamine mediated responses (examined by increased locomotion or stereotypy caused by systemically injected d-amphetamine), fluphenazine injected in the n. accumbens, but not in the striatum, significantly reduced the eating response elicited by muscimol in the NRD while food intake of deprived rats was not significantly modified by fluphenazine injected in either area. Fluphenazine (20 micrograms) in the striatum reduced eating in both conditions, but the animals showed marked sedation which obviously interfered with the feeding response. Dopamine release and synthesis, measured respectively by 3-methoxytyramine and accumulation of dihydroxyphenylalanine after aromatic amino acid decarboxylase inhibition, were significantly reduced in the n. accumbens, but not in the striatum, of muscimol treated animals. The metabolism of serotonin was reduced in both areas of muscimol treated rats. It is suggested that changes in dopamine receptor sensitivity, together with changes in serotonin function, might be involved in the feeding response caused by muscimol injection in the NRD.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1986

Neurochemical mechanism of action of drugs which modify feeding via the serotoninergic system.

The neurochemical mechanisms by which drugs acting on central serotoninergic system modify feeding were reviewed. Fenfluramine, a clinically effective appetite suppressant, releases serotonin from nerve terminals and inhibits its reuptake, and considerable evidence suggests that these effects mediate its anorectic activity. The D isomer of fenfluramine is particularly specific in affecting serotonin mechanisms and causing anorexia. Transmitters other than serotonin such as acetylcholine, catecholamines and GABA are also affected by systemic administration of fenfluramine, but some of these effects are secondary to fenfluramine's action on serotoninergic mechanisms. Moreover, there is no evidence that these brain substances are involved in fenfluramine's ability to cause anorexia. Several studies with drugs affecting different serotonin mechanisms such as release and uptake or mimicking the action of serotonin at post-synaptic receptors suggest that increase serotonin release and direct stimulation of postsynaptic receptors are the most effective mechanisms for causing depression of food intake, although inhibition of serotonin uptake may also contribute in appropriate conditions. Development of serotonin receptor hyposensitivity and, in some instances, decreased serotonin levels may lead to tolerance to the anorectic activity of drugs enhancing serotonin transmission, the degree of this depending critically on the type of effect on serotonin mechanisms and intensity and duration of serotonin receptor activation. Recent evidence suggests that a decrease in serotonin function causes stimulation of feeding. This may lead to development of new strategies for the treatment of clinical anorexias.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Hyperphagia caused by muscimol injection in the nucleus raphe dorsalis of rats: its control by 5-hydroxytryptamine in the nucleus accumbens.

Muscimol injection in the nucleus raphe dorsalis caused intense eating by rats with access to food. A dose-related reduction of muscimol's effect was found after bilateral injections of 5-hydroxytryptamine (5-HT) in the nucleus accumbens (dose range 2.2-8.8 micrograms in 2 microliter) but no effect was observed when an even higher dose (17.6 micrograms) of 5-HT was injected in the caudate putamen. Eating by food-deprived rats was not changed by any dose of 5-HT injected either into the nucleus accumbens or the caudate putamen. (+)-Norfenfluramine, 20 micrograms, injected in the nucleus accumbens also reduced muscimol-induced eating but had no effect on the food intake of starved rats. The results suggest an important role of 5-HT in the nucleus accumbens in the control of certain types of hyperphagia in rats.

Animals↗
PubMed1985

Salbutamol, d-amphetamine and d-fenfluramine reduce sucrose intake in freely fed rats by acting on different neurochemical mechanisms.

The effects of various doses of salbutamol, d-amphetamine and d-fenfluramine were studied on sucrose intake by freely-fed rats. All the drugs reduced sucrose consumption dose-dependently. Bilateral electrolytic lesions in the ventral noradrenergic bundle, which deplete hypothalamic noradrenaline, antagonized the effect of 1.25 mg/kg d-amphetamine on sucrose intake. A dose of 2.5 mg/kg d, 1-propranolol, a beta adrenergic blocker, prevented the effect of 10 mg/kg salbutamol but the dose of 5 mg/kg did not significantly change the effect of 0.6 or 1.25 mg/kg d-amphetamine. Captopril (35 mg/kg) reduced salbutamol's effect on water intake, but not on sucrose intake. Metergoline, 1 mg/kg, a central serotonin antagonist, but not xylamidine 2 mg/kg, a 5HT antagonist with limited access to the brain, counteracted the effect of 2.5 mg/kg d-fenfluramine on sucrose intake. These findings suggest a role for serotoninergic and adrenergic mechanisms in inhibiting ingestive behaviour maintained mainly by taste.

Albuterol↗
PubMed1984

Evidence that the dorsal raphe area is involved in the effect of clonidine against pentylenetetrazole-induced seizures in rats.

Injections of 5,7-dihydroxytryptamine (5,7-DHT) in the rat ventromedial tegmentum, which depleted forebrain serotonin, and of 6-hydroxydopamine in the dorsal noradrenergic bundle, which caused a marked reduction of forebrain noradrenaline, intensified pentylenetetrazol (PTZ)-induced seizures. Neither condition significantly modified the inhibitory effect of 0.5 mg/kg clonidine on PTZ-induced seizures, with the exception of the effect on mortality which was reduced in 5,7-DHT treated animals. Electrolytic lesions in the nucleus raphe medianus or dorsalis potentiated PTZ-induced seizures but only lesions in the nucleus raphe dorsalis significantly attenuated the effect of clonidine on tonic seizures and mortality. Both lesions reduced clonidine's effect on latency to the first convulsion. The results indicate that the dorsal raphe area plays a role in the inhibitory effect of 0.5 mg/kg clonidine on PTZ-induced seizures. Serotonin neurons other than those innervating diencephalic and telencephalic structures may also contribute, particularly to the effect of clonidine on tonic seizures.

5,7-Dihydroxytryptamine↗
PubMed1983

Monoamine involvement in the overeating caused by muscimol injection in the rat nucleus raphe dorsalis and the effects of d-fenfluramine and d-amphetamine.

Injections of 5,7-dihydroxytryptamine in the nucleus raphe dorsalis did not significantly modify the eating caused by muscimol (100 ng) injected in the same area of freely fed rats 11 days later. Eating caused by muscimol, like food intake in starved rats, was significantly reduced by phenoxybenzamine (5, 10 and 20 mg/kg i.p.). Penfluridol (2.5 and 5 mg/kg p.o.), a dopamine receptor blocker, markedly reduced muscimol-induced eating, but had no effect on the food intake of starved rats. d-Fenfluramine (2.5 mg/kg i.p.), a releaser of serotonin from nerve terminals, significantly reduced eating in muscimol-injected and starved animals whereas d-amphetamine 1.25 and 2.5 mg/kg i.p. only inhibited the food intake of starved rats. Eating elicited by muscimol injected in the nucleus raphe dorsalis appears to constitute a catecholamine-mediated model of hyperphagia selectively inhibited by agents which increase serotonin transmission.

5,7-Dihydroxytryptamine↗
PubMed1983

Studies on the mechanisms of tolerance to the anorectic effect of salbutamol in rats.

Two daily injections of 10 mg/kg salbutamol for 6 days caused complete tolerance in rats to the inhibitory effect on food intake measured 19 h after the last injection. Tolerance was not contingent on the time that elapsed between drug injections and eating during repeated treatment ('physiological' tolerance) and was reversible since the effect of salbutamol on food intake was completely reinstated 5 days after drug discontinuation. The anorectic effects of d-amphetamine and d-fenfluramine were not significantly modified in salbutamol tolerant animals, suggesting that the mechanisms involved in the tolerance to the effect of salbutamol are different from those involved in the effect of d-amphetamine and d-fenfluramine to cause depression of food intake in rats.

Adrenergic beta-Agonists↗
PubMed1983

The role of different types of adrenergic receptors in pentylenetetrazol-induced seizures and the effect of di-n-propylacetate in the rat.

Selective depletion of forebrain noradrenaline has been shown to potentiate various types of experimentally induced seizures. This study was aimed at exploring the role of different types of adrenergic receptors in pentylenetetrazol (PTZ)-induced seizures in rats and the anticonvulsive effect of di-n-propylacetate (DPA). Piperoxane (10 and 20 mg/kg, IP) significantly potentiated PTZ-induced tonic seizures and mortality. Similar effects were observed after 6-hydroxydopamine (6-OHDA)-induced depletion of forebrain noradrenaline, whereas no effects were found in animals with depletion of spinal noradrenaline. Neither phenoxybenzamine (20 mg/kg, IP) nor prazosin (1 and 10 mg/kg, IP) nor propranolol (2 and 5 mg/kg, IP) modified tonic seizures and mortality caused by PTZ. Combined treatment with propranolol (5 mg/kg, IP) and prazosin (10 mg/kg, IP) had no effect either. Various agents used to increase central serotonin transmission (d-fenfluramine, 5 mg/kg, IP; quipazine, 10 mg/kg, IP; m-chlorophenylpiperazine, 3 mg/kg, IP) did not alter the effect of piperoxane on PTZ-induced seizures. None of the conditions used to diminish central adrenergic function significantly affected the inhibitory effect of DPA on tonic seizures and mortality caused by PTZ. Combined treatment with subthreshold doses of clonidine (0.1 mg/kg, IP) and DPA (75 mg/kg, IP) significantly reduced tonic seizures and mortality caused by PTZ. The data suggest that alpha 2 type adrenoceptors are involved in the control of PTZ-induced seizures in rats. The peculiarity of the role of these receptors in the effect of PTZ is discussed.

Animals↗
PubMed1983

Studies on the role of serotonin in different regions of the rat central nervous system on pentylenetetrazol-induced seizures and the effect of di-n-propylacetate.

5,7-Dihydroxytryptamine (5,7-DHT) injections which caused selective depletion of serotonin in the forebrain enhanced the seizures caused by pentylenetetrazol (PTZ 90 mg/kg s.c.) in rats. No effect was observed in rats with 5,7-DHT-induced depletion of spinal serotonin or treated with metergoline (1 mg/kg i.p.) or methysergide (10 mg/kg i.p.). The various procedures aimed at decreasing serotonin transmission did not significantly modify the effect of di-n-propylacetate (DPA) on tonic seizures and mortality caused by PTZ but significantly reduced the DPA-induced increase in the latency to the first convulsion. More animals with clonic seizures were seen in the DPA-treated group which had been subjected to selective depletion of spinal serotonin or treated with methysergide than in DPA-treated controls. Combined treatment with d-fenfluramine (1.25 mg/kg i.p.) and DPA (75 mg/kg i.p.), doses which by themselves had no significant effect, reduced tonic seizures and mortality caused by PTZ. The results show that a diffuse deficit in forebrain serotonin enhances PTZ-induced seizures. Serotonin does not play an important role in the effect of DPA against PTZ-DPA on clonic convulsions. Agents increasing serotonin transmission may enhance the anticonvulsant activity of DPA.

5,7-Dihydroxytryptamine↗
PubMed1982

Evidence that systemically administered salbutamol reduces food intake in rats by acting on central beta-adrenergic sites.

Salbutamol was found to reduce food intake in a dose-related manner. The effect was prevented by the beta-adrenolytic drugs d,1-propranolol and d,1-alprenolol. In contrast, phentolamine, penfluridol and metergoline, which block alpha-adrenergic, dopamine and serotonin receptors respectively, or bilateral lesions of the ventral noradrenergic bundles were not able to counteract salbutamol's effect. The reduction of food intake induced by salbutamol was prevented by intracerebroventricular administration of d,1-propranolol. In addition, salbutamol was found to effectively reduce the apparent motivation for food as revealed by its effect on food-rewarded runaway behaviour. This effect was also counteracted by d,1-propranolol pretreatment. The findings indicate that food intake may be reduced by peripheral administration of salbutamol and that the effect is mediated by stimulation of central beta-adrenergic sites.

Albuterol↗
PubMed1982

d-Amphetamine-induced anorexia and motor behavior after chronic treatment in rats: relationship with changes in the number of catecholamine receptor sites in the brain.

No tolerance to the anorectic activity of d-amphetamine was found in rats given two daily injections of 1.25 mg/kg for 28 days. Such rats also presented no changes in the number of binding sites for serotonin and catecholamines in various brain areas. A 28-day treatment with 10 mg/kg d-amphetamine twice daily caused a significant reduction in the number of binding sites for 3H-dihydroalprenolol (beta adrenergic receptor ligand) in hippocampus, and 3H-spiroperidol (dopamine receptor ligand) in striatum and nucleus accumbens. This treatment did not modify the anorectic effect of 1.25 mg/kg of amphetamine but it markedly reduced the motor hyperactivity induced by this treatment and completely blocked the stereotyped licking and biting induced by apomorphine. Amphetamine stereotypy was not significantly reduced but disappeared faster in chronically treated rats. The possible reasons for the different results (tolerance or sensitization) reported by various authors on changes in amphetamine's effects on motor behaviour during chronic treatment are discussed.

Animals↗
PubMed1981

Immobility test: effects of 5-hydroxytryptaminergic drugs and role of catecholamines in the activity of some antidepressants.

Fenfluramine and m-chlorophenylpiperazine, two drugs purported to enhance central 5-hydroxytryptaminergic transmission, and metergoline, a 5-HT antagonist, did not modify the duration of immobility induced in rats made to swim in a restricted space. Nomifensine, desipramine and amineptine, three antidepressants known to block neuronal catecholamine uptake, significantly reduced the duration of immobility. Penfluridol, a dopamine antagonist at central receptors, counteracted the effect of nomifensine and amineptine but not that of desipramine. Propranolol and phenoxybenzamine respectively reduced the effects of desipramine and nomifensine but did not modify amineptine's effect. Metergoline pretreatment did not counteract the effect of any drug. The results indicate that various antidepressants can reduce the duration of immobility in rats by activating dopaminergic and/or noradrenergic mechanisms in the brain. Either alpha- or beta-noradrenergic receptors could contribute to the anti-immobility effects, depending on the drug used. The immobility test appears to be insensitive to drugs activating or reducing 5-HT-ergic mechanisms in the brain.

Animals↗
PubMed1980

Hyper- and hyposensitivity of central serotonin receptors:[3H]serotonin binding and functional studies in the rat.

The effect of repeated treatment with D-fenfluramine, a serotonin releaser, or methergoline, a serotonin antagonist, on [3H]5-HT binding was studied in various rat brain areas. In animals with the same pretreatments, the anorectic activity of m-chlorophenylpiperazine, a serotonin agonist, was investigated. A 14-day treatment with D-fenfluramine caused a significant decrease in the number of [3H]5-HT binding sites (Bmax) in the diencephalon. A reduction of binding sites was found in the cortex too when D-fenfluramine was administered for 28 days. Methergoline caused no changes of [3H)5-HT binding in any brain area examined when given for 14 days but 28-day treatment led to a significant increase in the striatum, hippocampus and cortex. D-Fenfluramine and methergoline caused, respectively, a decrease and increase in the effect of m-chlorophenylpiperazine on food intake. The data show that central 5-HT receptor numbers and sensitivity may change after repeated treatments with drugs acting on brain serotonin.

Animals↗
PubMed1980

Repeated treatment with d-fenfluramine or metergoline alters cortex binding of 3H-serotonin and serotenergic sensitivity in rats.

28-day treatment with d-fenfluramine, a serotonin (5HT) releaser and uptake inhibitor, caused significant reduction (23%) of 3H-5HT binding sites (Bmax) in the rat cortex. These sites were significantly increased (31%) in cortical membranes of rats which had received metergoline, a potent serotonin antagonist, for 28 days. Parallel changes were found in the anorectic activity of metachlorophenylpiperazine (m-CPP), a potent central 5HT agonist: chronic treatment with d-fenfluramine or metergoline caused respectively a decrease and in the effect of m-CPP on food intake. The data show that changes in 5HT central receptor number and sensitivity may occur after chronic treatment with drugs acting on brain serotonin.

Animals↗
PubMed1980

Further studies on the mechanism of serotonin-dependent anorexia in rats.

4-(3-Indolyl-2-ethyl) piperidine (LM 5008), 2-(1-piperazinyl) quinoline (quipazine), and metachlorophenylpiperazine (mCPP) were studied for their ability to affect serotonergic mechanisms in vitro. Their relative potency in inhibiting serotonin (5-HT) uptake in vivo and reducing food intake in rats was also examined. mCPP was very potent in displacing 3H-5-HT bound to brain membranes (IC50, 6.2 X 10(-7) M), followed by quipazine, which showed an IC50 of 3.8 X 10(-6) M. LM 5008 was the least effective with an IC50 of 3.6 X 10(-5) M. mCPP and quipazine were less potent than d-fenfluramine in releasing 14C-5-HT from brain synaptosomes, while LM 5008 caused no significant effects at a concentration of 10(-5) M. Conversely, both in vitro and in vivo studies on 5-HT uptake showed that LM 5008 was the most potent compound in inhibiting 5-HT uptake and mCPP the least potent. Since a 50% reduction of food intake was not reached even with a dose of LM 5008 27-times higher than the ED50 for inhibiting 5-HT uptake in vivo, it is suggested that even marked inhibition of 5-HT uptake at central synapses is not sufficient per se to trigger serotonin-dependent anorexia in the rat. Increased release and/or direct stimulation of post-synaptic receptors may be necessary to obtain this effect. This could be of interest for developing new agents which can cause anorexia by interacting with brain serotonin.

Animals↗