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F Borsini

Publications and source records attributed to F Borsini.

At least 55 records · Page 3Linked to original sources
PubMed1991

Evidence that imipramine activates 5-HT1C receptor function.

The anti-immobility effect of imipramine (15 mg/kg) in the forced swimming test in mice was antagonized by the non-selective 5-hydroxytryptamine (5-HT) antagonist, metitepine (0.5 mg/kg), by the 5-HT1C/5-HT2 antagonist, mesulergine (15 mg/kg), and by the dopamine D2 antagonist, d,l-sulpiride (50 mg/kg). These three antagonists did not alter the behaviour of imipramine-treated mice in an open-field and did not reduce imipramine brain levels. The 5-HT2 antagonist, ritanserin (0.06 mg/kg), the 5-HT1A/5-HTB antagonist, l-propranolol (20 mg/kg), and the 5-HT3 antagonists, endo-2,3-dihydro-N-(8-methyl-8-azabicyclo[3.2.1]oct-3-yl)-2-oxo-1H- benzimidazole-1-carboxamide hydrochloride (DAU 6215; 0.1 mg/kg) and 1,2,3,9-tetrahydro-9-methyl-3[(2-methyl-1H-imidazol-1-yl)methyl]-4H- carbazol-4-one, HCl.2H2O) (GR 38032F; 0.1 mg/kg), failed to reduce imipramine-induced anti-immobility. Subthreshold doses of 8-hydroxy-2-(di-n-propylamino)tetralin hydrochloride (8-OH-DPAT; 0.5 mg/kg) and imipramine (7.5 mg/kg) did not synergize in reducing immobility. d,l-Sulpiride, but not mesulergine, antagonized the effect of desipramine (15 mg/kg) in the forced swimming test. All compounds were administered i.p. 6 min before imipramine or desipramine, given i.p. 30 min before the testing. Imipramine produced 50% inhibition of [3H]mesulergine binding to 5-HT1C receptors at 10 microM, a concentration below that obtained following i.p. imipramine administration. The results suggest a contribution of 5-HT1C receptors in the mechanism of the imipramine effect in the forced swimming test.

Animals↗
PubMed1991

Effect of psychotomimetics and some putative anxiolytics on stress-induced hyperthermia.

Stress-induced hyperthermia (SIH), which is seen in the last mice removed from the cage, is a novel animal model sensitive to anxiolytic drugs. SIH is antagonized by CL 218872 (25 and 50 mg/kg, os), by tracazolate (5 and 7.5 mg/kg, ip) and by 2-AP-5 (50 and 100 mg/kg, ip). At higher dose, CL 218872 (100 mg/kg, os) and tracazolate (12.5 mg/kg, ip) lose their activity. PK 9084 (5-40 mg/kg, ip) and CGS 9896 (2-20 mg/kg, both ip and os) were also ineffective in preventing SIH. The anti-hyperthermic effect of CL 218872 (25 mg/kg) and tracazolate (7.5 mg/kg) was blocked by the benzodiazepine antagonist Ro 15-1788 (15 mg/kg), CGS 9896 (10 mg/kg, os) also reversed the effect of CL 218872 (25 mg/kg) on SIH. Differently from anxiolytics, MK-801 (0.5-1 mg/kg, os), PCP (2.5 mg/kg, ip) and d-amphetamine (10 mg/kg, ip) evoked hyperthermia in the first set of mice and prevented a further stress-induced rise of body temperature in the last set of mice.

2-Amino-5-phosphonovalerate↗
PubMed1991

Effect of enantiomers of propranolol on desipramine-induced anti-immobility in the forced swimming test in the rat.

The effect of d- and l-enantiomers of propranolol on desipramine-induced anti-immobility effects and on brain desipramine levels was studied in the rat. Intraperitoneal propranolol and desipramine were administered three times, 25, 6, 2 and 24, 5, 1 h respectively, before the test. It was found that l-propranolol but not d-propranolol, at the same doses (2.5 and 5 mg/kg), antagonized 20 mg/kg desipramine without altering desipramine brain levels. It is suggested that blockade of beta-adrenergic receptors rather than membrane-stabilizing or pharmacokinetic effects is responsible for the antagonism of propranolol toward desipramine.

Animals↗
PubMed1991

New dibenzothiadiazepine derivatives with antidepressant activities.

A new series of 11-[(aminoalkyl)carbonyl] derivatives of 6,11-dihydrodibenzo[c,f][1,2,5]thiadiazepine 5,5-dioxide (10-39) were synthesized and evaluated for potential antidepressant activity in the apomorphine-induced hypothermia (Apo 16) test. Effects on reserpine-induced hypothermia and toxicity for the most potent antagonists of Apo 16 hypothermia were also studied. Structure-activity relationships are reported. Anticholinergic effects were evaluated for compound 12, identified as the most potent and least toxic in this series, by assessing physostigmine lethality. Compound 12 was also subjected to X-ray analysis.

Animals↗
PubMed1991

Potential antidepressant activity and enhancement of serotonin uptake of a new dibenzothiadiazepine derivative.

A molecule, 6-methyl-6,11-dihydro-11-[(N,N-dimethylamino) acetyl]dibenzo[c,fl-[1,2,5]thiadiazepine 5,5-dioxide, (IM/P/3/4, CAS 128377-70-8), was identified in a screening program, which had the scope of finding compounds with antidepressive potential without the common sideeffects of existing antidepressive medication. IM/P/3/4 was found active a) in antagonizing apomorphine (16 mg/kg) and reserpine-induced hypothermia in mice; b) in potentiating yohimbine-induced lethality in mice; c) in reducing immobility of rats forced to swim and of mice suspended by the tail. IM/P/3/4 does not affect a) apomorphine-induced stereotypy; b) amphetamine-induced hypermotility; c) haloperidol-induced catalepsy and water-induced grooming and d) does not induce stereotypy or alter motor activity. The compound also a) reduced the beating of rat right heart atria only at a concentration of 3 x 10-4 mol/l; b) had weak anticholinergic activity; c) antagonized electroshock-induced convulsions and d) prevented indometacin-induced duodenal ulcers. IM/P/3/4 does not have good affinity for noradrenergic, serotonergic, dopaminergic, histaminergic or muscarinic receptors and does not displace imipramine, desipramine and mianserine from their binding sites. IM/P/3/4 increases 5-hydroxyindolacetic acid content and 3H-serotonin uptake in the hypothalamus. The present results suggest that IM/P/3/4 is a potential antidepressant with reduced side effects and with a mechanism of action which is different from that of other antidepressants.

Anesthetics↗
PubMed1990

Effect of serotoninergic drugs on stress-induced hyperthermia (SIH) in mice.

8-OH-DPAT (2.5-10 mg/kg) and buspirone (10 mg/kg) but not 5,7-DHT (200 micrograms/mouse), pCPA (75 and 150 mg/kg, three times), ritanserin (0.1 and 0.2 mg/kg), LY 53857 (1.5 and 3 mg/kg), GR 38032 F (0.1-100 micrograms/kg), TFMPP (5 and 20 mg/kg) and mCPP (2.5 and 5 mg/kg) antagonized the rise in body temperature that occurs to the last mice removed from their group housing, which was termed as stress-induced hyperthermia (SIH). Ro 15-1788, at a dose which blocked the effect of diazepam on SIH, did not reverse the anxiolytic effect of buspirione. Instead, when cerebral 5-HT content was reduced to 50% by 5,7-DHT-induced lesion, the effect of buspirone on SIH was decreased. TFMPP 5 mg/kg did not shorten significantly the onset of SIH as could have been expected by an anxiogenic drug, while the dose of 20 mg/kg did not modify the pattern of SIH at all. The lower dose of TFMPP evoked a hyperthermic and the higher a hypothermic response.

5,7-Dihydroxytryptamine↗
PubMed1990

Pharmacological validation of a novel animal model of anticipatory anxiety in mice.

The current study investigates the action of anxiolytics, antidepressants, neuroleptics, antipyretics, muscle relaxants, antihypertensives and naloxone in a novel animal model of anxiety, based on the evidence that mice removed last from their cage develop hyperthermia (stress-induced hyperthermia, SIH) when compared to those removed first. Alprazolam (0.15-0.6 mg/kg), chlordiazepoxide (25 mg/kg), estazolam (1 mg/kg), phenobarbital (20 mg/kg), ethanol (2 and 4 g/kg), buspirone (5 and 10 mg/kg) and prazosin (1 and 2 mg/kg), as well as repeatedly administered diazepam (5 mg/kg), inhibited SIH. In contrast, tofisopam (12.5-200 mg/kg), desipramine (15 and 30 mg/kg), amitriptyline (10 mg/kg), fluoxetine (10 and 20 mg/kg), tranylcypromine (5 and 10 mg/kg), chlorpromazine (1 and 2 mg/kg), clozapine (2 and 4 mg/kg), pimozide (0.5 and 1 mg/kg), l-sulpiride (15 and 30 mg/kg), l-propranolol (5 and 10 mg/kg), acetyl salicylic acid (200 and 400 mg/kg), indomethacin (2.5 and 5 mg/kg), verapamil (2.5 and 5 mg/kg), captopril (25 and 50 mg/kg), dantrolene (10 and 20 mg/kg), mephenesin (300 and 600 mg/kg), d-amphetamine (1 and 4 mg/kg) and naloxone (2.5 and 15 mg/kg) were inactive, as were 10 mg/kg imipramine, amitriptyline and fluoxetine injected every day for 21 days. Reserpine at high doses (1.25 and 2.5 mg/kg) but not at a lower dose (0.62 mg/kg) prevented SIH, but in this case animals showed a behavioural syndrome which could have interfered with the occurrence of the hyperthermia.

Animals↗
PubMed1990

Desipramine and nortriptyline antagonize apomorphine and reserpine hypothermia by a different mechanism.

The reversal of hypothermia, induced by reserpine or by a high (16 mg) dose of apomorphine, in male Swiss mice, does not seem to utilize a common mechanism. Desipramine (20 mg kg-1 i.p., 60 min) or nortriptyline (8 mg kg-1 i.p., 60 min) increased temperature in both reserpine (2.5 mg kg-1 s.c., 18-19 h) and apomorphine (16 mg kg-1 s.c., 30 min) treated mice. In apomorphine-treated animals the effect of both drugs was reversed by the mixed dopaminergic D1- D2-antagonist haloperidol (1 mg kg-1 i.p., 90 min), the D1-receptor blocking drug SCH 23390 (0.05 mg kg-1 s.c., 30 min), the alpha 1-adrenoceptor blocking drugs prazosin (3 mg kg-1 s.c., 90 min) and phenoxybenzamine (20 mg kg-1 i.p., 65 min), the beta-adrenoceptor blocking drug (+/-)-propranolol (10 mg kg-1 i.p., 120 min), and the opioid antagonist naloxone (2 mg kg-1 i.p., 15 min). In contrast the selective D2-antagonist (+/-)-sulpiride (100 mg kg-1 i.p., 90 min), and the alpha 2-antagonist yohimbine (2 mg kg-1 i.p., 75 min), failed to effect the reversal of apomorphine hypothermia brought about by desipramine or nortriptyline. Their temperature effects in reserpinized mice were not modified by any of the antagonists tested.

Animals↗
PubMed1989

Discovery of antidepressant activity by forced swimming test may depend on pre-exposure of rats to a stressful situation.

Antidepressant-induced anti-immobility effects have been assessed in animals exposed or not to a pretest session using the forced swimming test. Desipramine, maprotiline, mianserine (15 and 30 mg/kg), nomifensine (2.5 and 5 mg/kg), d-amphetamine (1 and 2 mg/kg) and muscimol (1 and 2 mg/kg), unlike imipramine (15 and 30 mg/kg), LY-171555 (0.1 and 0.2 mg/kg) and scopolamine (0.5 and 0.1 mg/kg), did not reduce immobility time in rats which had not received the pretest session. On the other hand, all of the drugs tested reduced immobility time in rats exposed to a pretest session. In addition, the degree of antiimmobility effects of desipramine (20 mg/kg) and nomifensine (5 mg/kg) increased proportionally with the level of water (0, 4, 15 and 30 cm) to which animals were exposed at the time of pretest. Furthermore, desipramine reduced immobility time in rats pre-exposed to types of stress different from forced swimming, cold, restraint or foot-shock. All drugs were injected intraperitoneally three times, 24, 5 and 1 h before testing. The present findings suggest that a stressful pretest session may reveal pharmacological properties of antidepressants in the forced swimming test. This is also substantiated by the fact that diazepam (2.5 and 5 mg/kg) administered 30 min before the swimming pretest antagonized the anti-immobility effect of 15 mg/kg desipramine.

Animals↗
PubMed1989

A model to measure anticipatory anxiety in mice?

Among animals from the same cage, mice removed last had a higher temperature compared to those removed first. This phenomenon a) persisted 2 and 24 h later; b) was present regardless of the number of the animals (5, 10, 15 and 20) in each cage, c) was independent of whether the number of animals was reduced or maintained constant in the cage and d) could even be observed by reversing the order of removal of the animals from the cage. In addition, the fewer the animals allocated to a cage the greater the percentage of those which became hyperthermic. This rise in rectal temperature of mice removed last was prevented by diazepam (2.5 and 5 mg/kg PO, 30 min), nitrazepam (2 and 4 mg/kg PO, 30 min) but not by imipramine (15 and 30 mg/kg PO, 60 min) or haloperidol (0.5 and 1 mg/kg PO, 60 min) and was observed in a greater percentage of mice following subcutaneous yohimbine treatment (2 mg/kg, 60 min). This phenomenon does not seem to depend on physical exercise due to an attempt to escape, since no correlation appears to exist between motor activity (open-field) and rise in rectal temperature. These data would seem to indicate that hyperthermia in the last animals may represent a new tool for studying the neurobiology of anticipatory(?) anxiety.

Animals↗
PubMed1989

Experimental procedure to favor an otherwise undetectable potential rat muricidal behavior.

We hypothesized that variation in mouse aggressiveness could, at least in part, affect muricidal attitude of rats, therefore we introduced a sedated (diazepam 50 mg/kg/PO) instead of a normal (nonsedated) mouse into a cage with a rat. Rats were challenged with sedated or nonsedated mice for two-four days. It was found that a) the percentage (40-60%) of rats which killed a sedated mouse was higher than that (about 10%) of those which killed a nonsedated mouse; b) rats trained to kill a sedated mouse did not kill a nonsedated mouse and c) rats which did not kill a nonsedated mouse did not kill a sedated mouse. The present results indicate that the first experience in the presence of a sedated mouse uncovers a muricidal behavior which persists upon exposure to subsequent similar experimental conditions. This behavior undergoes seasonal variations, reaching a maximum in September-October and a minimum in February-March.

Aggression↗
PubMed1989

Effect of acute or chronic administration of imipramine on spinal and supraspinal micturition reflexes in rats.

Acute imipramine administration (15 mg/kg i.p. 60 min before) increased the threshold for activating the spinal but not the supraspinal vesico-vesical micturition reflex in urethane-anesthetized rats. On the other hand, "chronic" imipramine administration (15 mg/kg i.p./day for 5 consecutive days) increased selectively the threshold of the supraspinal micturition reflex. Intravenous administration of cumulative doses of imipramine (up to 14 mg/kg) exerted a progressive inhibitory effect on the supraspinal reflex and voiding efficiency, possibly related to direct inhibition of muscular contractility at the bladder level. However, with the dose regimen used to compare the action of imipramine on spinal and supraspinal reflexes (15 mg/kg i.p., 60 min before), imipramine did not affect the volume-pressure curve or myogenic activity in decentralized bladders (bilateral removal of pelvic ganglia). The effect of acute imipramine on threshold of the spinal vesico-vesical reflex was absent in rats receiving oral p-chlorophenylalanine to deplete 5-hydroxytryptamine stores in the central nervous system. On the other hand, p-chlorophenylalanine pretreatment did not prevent the action of chronic imipramine administration on the supraspinal reflex. Acute administration of desipramine, the major metabolite of imipramine, increased threshold of the spinal but not supraspinal micturition reflex. These findings indicate that the ability of imipramine to modulate vesico-urethral motility at the central nervous system level may involve different mechanisms. Inhibition of 5-hydroxytryptamine reuptake in nerve terminals may be important for the acute modulatory effect of imipramine on the spinal reflex.

Animals↗
PubMed1989

Pharmacological profile of the new anticonvulsant etazepine.

The pharmacological profile of the new anticonvulsant etazepine (5,6-dihydro-5-methyl-11H-11-ethoxy-dibenzo[b,e]azepin-6-one) was investigated. It protected mice and rats from a wide variety of convulsant agents (maximal electroshock, pentetrazol (metrazole), bicuculline, strychnine, 3-mercaptopropionic acid, nicotine, cefazoline and kainic acid) at doses about 16-45 times lower than those exerting neurotoxic effects (depending on the test used). The anticonvulsant effect of etazepine was long-acting (more than 24 h) and did not seem to develop tolerance. Moreover, etazepine did not prolong thiopental-induced sleeping time. Based on pharmacological studies etazepine seems to exert its anticonvulsant effects by activating the GABAergic system.

5-Hydroxytryptophan↗
PubMed1988

Cholinergic drug effects on antidepressant-induced behaviour in the forced swimming test.

The contribution of anticholinergic effects to the action of desipramine and nomifensine was investigated in the forced swimming test in rats. The immobility time was reduced by high doses of atropine (10-25 mg/kg i.p.) and scopolamine (1.5 mg/kg i.p., 1 and 0.5 h before the test, respectively) and was unaffected by physostigmine (0.25-0.5 mg/kg i.p., 1 h before the test). Unlike atropine (25 mg/kg), scopolamine (1.5 mg/kg) increased motor activity (open-field). The anti-immobility effect of i.p. desipramine (20 or 30 mg/kg) and nomifensine (2.5 or 5 mg/kg), administered 24, 5 and 1 h before the test, was potentiated by scopolamine (0.5-1.0 mg/kg) and antagonized by physostigmine (0.25-0.5 mg/kg). The brain levels of desipramine and nomifensine were unaffected by scopolamine or physostigmine. Motor performance was impaired in rats treated with physostigmine and desipramine whereas hypermotility was observed in rats treated with scopolamine and nomifensine. The anti-immobility effect of atropine (25 mg/kg) and scopolamine (1.5 mg/kg) was not antagonized by physostigmine (0.5 mg/kg). These results indicate that anticholinergic mechanisms alone are not sufficient to influence immobility time and suggest that the cholinergic system may control, the neural circuitry upon which desipramine and nomifensine act to reduce immobility time.

Animals↗
PubMed1988

The effect of 4-aminopyridine on micturition reflex in normal or capsaicin-desensitized rats.

4-aminopyridine (4-AP) produced a dose-related (0.15-2 mg/kg i.v.) potentiation of the voiding cycle of the urinary bladder and increased frequency of micturition in urethane-anesthetized rats. In bladders containing a subthreshold amount of fluid for eliciting reflex micturition 4-AP (1-3 mg/kg i.v.) activated a series of high-amplitude, hexamethonium-sensitive rhythmic bladder contractions. In rats desensitized to capsaicin as newborns, reflex micturition was almost abolished: in these animals i.v. 4-AP did not affect bladder voiding unless at high doses (1-2 mg/kg), at which a reversal from anesthesia occurred. This was accompanied by a prompt micturition. In unanesthetized rats, neither the 4-AP-induced convulsions nor the behavioral response (assessed in an open field) to 4-AP were affected by neonatal capsaicin desensitization. Daily urine production of capsaicin-pretreated animals did not differ from that of controls. However, when measurements were made during daytime, almost no spontaneous urine emission was found in capsaicin-treated rats. On the rat isolated urinary bladder, 4-AP potentiated the response to field stimulation in preparations from both vehicle- and capsaicin-pretreated animals. These findings indicate that 4-AP has a potent excitatory action on bladder voiding in rats and support the hypothesis that in this species 'conscious' bladder voiding can be initiated through capsaicin-resistant mechanisms.

4-Aminopyridine↗
PubMed1988

Stimulation of dopamine D-2 but not D-1 receptors reduces immobility time of rats in the forced swimming test: implication for antidepressant activity.

The involvement of dopamine D-1 and D-2 receptor mechanisms was investigated in the forced swimming test with rats. d,1-Sulpiride, a D-2 receptor antagonist, reported to reduce desipramine-induced anti-immobility, did not alter the brain levels of desipramine. In addition, the anti-immobility effect of desipramine was not antagonized by SCH 23390, a D-1 receptor antagonist. Amineptine (20 mg/kg i.p., 60 min before testing), a dopamine uptake blocker, and LY171555 (0.2 mg/kg i.p., 60 min before testing), a dopaminergic D-2 stimulant reduced immobility time in the forced swimming test, but benserazide + 1-DOPA (200 mg/kg p.o., 45 min before testing), which increases dopamine release, or SKF 38393A (20 mg/kg s.c., 60 min before testing), a D-1 agent, did not. The anti-immobility effect but not the stereotypy was increased following chronic (21 days) LY171555 (0.1 and 0.2 mg/kg i.p.) treatment. The effect of acute or repeated (7 days) LY171555 (0.2 mg/kg i.p.) treatment was antagonized by 1-sulpiride (50 mg/kg i.p., 90 min before testing), a D-2 receptor antagonist. Neither SKF 38393A (20 mg/kg s.c., 60 min before testing) nor SCH 23390 (0.05 mg/kg s.c., 30 min before testing) modified the acute anti-immobility effect of LY171555 (0.2 mg/kg i.p.) SCH 23390 (0.025 and 0.05 mg/kg) increased the immobility time at doses which decreased motor activity. The increase in immobility time brought about by SCH 23390 was not antagonized by SKF 38393A (20 mg/kg). The findings indicate that activation of dopamine D-2 receptors could reduce immobility time.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗