Search PubMed⌕ Search

Biomedical subjects

F Borsini

Publications and source records attributed to F Borsini.

87 records · Page 5Linked to original sources
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↗
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↗
PubMed1979

Chlorophenylpiperazine: a central serotonin agonist causing powerful anorexia in rats.

Meta-chlorophenylpiperazine inhibited serotonin and noradrenaline uptake by synaptosomes to the same extent with IC50 of 1.3 x 10(-6) M and 5.8 x 10(-6) M respectively. Dopamine uptake was less affected by meta-chlorophenylpiperazine (IC50 of 2.2 x 10(-5) M). Unlike d-amphetamine and d-fenfluramine, the drug did not significantly increase monoamine release in synaptosomal preparations. On the other hand, metachlorophenylpiperazine showed an IC50 of 620 nM in displacing 3H-5HT binding to brain membranes. Meta-chlorophenylpiperazine produced a dose-dependent reduction of food intake and this effect was prevented by a pretreatment with methergoline, a serotonin antagonist. The effect of metachlorophenylpiperazine was not modified by an intraventricular injection of 6-hydroxydopamine, electrolytic lesions of nucleus medianus raphe or ventral noradrenergic bundle, nor by a pretreatment with penfluridol, propranolol or phentolamine. The data suggest that the decrease of food intake induced by metachlorophenylpiperazine depends on its ability to act as a serotonin agonist is the brain. The specificity of the effects on serotonin suggests that this compound could prove an important tool for studies aimed at elucidating the functional role of serotonin in the central nervous system.

Animals↗
PubMed1979

The roles of brain noradrenaline and dopamine in the anorectic activity of diethylpropion in rats: a comparison with d-amphetamine.

The anorectic activity of diethylpropion and d-amphetamine was studied in rats subjected to various treatments known to affect brain monoamines. The effect of diethylpropion, like that of d-amphetamine, was completely prevented by a lesion of the ventral noradrenergic bundle, which selectively decreases brain noradrenaline, but was not significantly modified in desipramine pretreated rats by an intraventricular injection of 6-hydroxydopamine, a condition decreasing only dopamine. Pretreatment with penfluridol significantly reduced the effect of d-amphetamine but not that of diethylpropion. A non-significant reduction of drug effect was found with alpha-methyl-p-tyrosine. Lesion of the nucleus medianus raphe, which destroys central serotonin neurons, or treatment with methergoline, a central serotonin antagonist, caused no changes in the effects of both compounds. The findings show that integrity of central noradrenergic neurons is an important condition for diethylpropion and d-amphetamine to exert their anorectic effect. Dopamine does not seem to play any role in the effect of diethylpropion but might contribute to that of d-amphetamine. The data are against any involvement of brain serotonin in diethylpropion anorexia.

Animals↗
PubMedDate not supplied

The effect of DAU 6215, a novel 5HT-3 antagonist, in animal models of anxiety.

The aim of the present study was to evaluate the effect of DAU 6215 (N-(endo-8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2, 3-dihydro-2-oxo-1H-benzimidazol-1-carboxamide, hydrochloride), which is a 5HT-3 receptor antagonist, chemically different from the other 5HT-3 antagonists, on a wide variety of animal models sensitive to anxiolytics. Nine animal models were used. DAU 6215 was active in reducing (i) aversion to a brightly lit environment in the light/dark exploratory test in mice, (ii) unpleasant properties of an aversive drug in rats (naloxone-induced place aversion), and (iii) aggressiveness in monkeys. DAU 6215 was effective at doses ranging (a) between 10 and 1000 micrograms/kg given i.p. in mice, (b) between 15 and 30 micrograms/kg given s.c. in rats and (c) between 1 and 10 micrograms/kg given orally in monkeys. DAU 6215 was inactive in (iv) the elevated plus maze, (v) conflict test and (vi) emotional hypophagia in rats and in (vii) the four plates test, (viii) staircase test and (ix) stress-induced hyperthermia in mice. Diazepam was active in all tests. In contrast to diazepam, DAU 6215 did not induce place preference, suggesting the possible lack of addictive properties.

Animals↗
PubMedDate not supplied

Is there a relationship between rat latent aggressiveness and susceptibility to convulsive crises?

Experiments were aimed at assessing a possible different sensitiveness to seizures in aggressive vs. nonaggressive rates. Thirty-nine muricidal rats were selected by using a sedated mouse. Six of these killer rats (K) showed electroencephalographic (EEG) spontaneous syncronous wave-and-spike discharges, 6-11 c/s. None of nonkiller animals (NK) showed a similar pattern. These 6 K were not used for the subsequent experiments. Intraperitoneal pentylentetrazole (PTZ; 10, 20, and 40 mg/kg) or bicuculline (BIC; 2 and 4 mg/kg) was given to both NK and K. K were more sensitive than NK to the epileptogenic effects of 20 mg/kg PTZ and 2 mg/kg BIC, as revealed by the significant increased number of convulsive rats and longer duration of EEG seizures. No difference in EEG or convulsant behavior was observed between K and NK after the administration of the lower dose of PTZ and the high dose of PTZ or BIC. The use of K rats as a possible new sensitive model of petit mal is discussed.

Aggression↗
PubMedDate not supplied

DAU 6215, a novel 5-HT3 receptor antagonist, improves performance in the aged rat in the Morris water maze task.

The effects of the new 5-HT3 receptor antagonist, DAU 6215, on aged rats' cognition were assessed in the Morris water maze task. Task performance of aged animals that received acutely the dose of 10 micrograms/kg IP was not different than that of their aged controls treated with the vehicle. Conversely, a repeated IP administration of 10 micrograms/kg DAU 6215 for 3 weeks significantly improved task performance of the aged animals as compared to that displayed by the old rats treated with the vehicle.

Aging↗