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F Nava

Publications and source records attributed to F Nava.

At least 19 recordsLinked to original sources
PubMed2001

An anorexic lipid mediator regulated by feeding.

Oleylethanolamide (OEA) is a natural analogue of the endogenous cannabinoid anandamide. Like anandamide, OEA is produced in cells in a stimulus-dependent manner and is rapidly eliminated by enzymatic hydrolysis, suggesting a function in cellular signalling. However, OEA does not activate cannabinoid receptors and its biological functions are still unknown. Here we show that, in rats, food deprivation markedly reduces OEA biosynthesis in the small intestine. Administration of OEA causes a potent and persistent decrease in food intake and gain in body mass. This anorexic effect is behaviourally selective and is associated with the discrete activation of brain regions (the paraventricular hypothalamic nucleus and the nucleus of the solitary tract) involved in the control of satiety. OEA does not affect food intake when injected into the brain ventricles, and its anorexic actions are prevented when peripheral sensory fibres are removed by treatment with capsaicin. These results indicate that OEA is a lipid mediator involved in the peripheral regulation of feeding.

Animals↗
PubMed2001

gamma-Hydroxybutyric acid and baclofen decrease extracellular acetylcholine levels in the hippocampus via GABA(B) receptors.

The effect of gamma-hydroxybutyric acid (GHB) and baclofen, a GABA(B) receptor agonist, on extracellular hippocampal acetylcholine levels was studied in freely moving rats by microdialysis. GHB (200 and 500 mg/kg, i.p.) reduced in a dose-dependent manner, extracellular hippocampal acetylcholine concentrations and this effect was prevented by the GABA(B) receptor antagonist (2S)(+)-5,5-Dimethyl-2-morpholineacetic acid (SCH 50911), at the dose of 20 mg/kg (i.p.), while the putative GHB receptor antagonist 6,7,8,9-Tetrahydro-5-hydroxy-5H-benzocyclohept-6-ylideneacetic acid (NCS 382) was ineffective. Similar to GHB, the GABA(B) agonist baclofen (10 and 20 mg/kg, i.p.) produced a dose-related reduction in extracellular acetylcholine concentrations which was prevented by SCH 50911. These findings indicate that GHB-induced reduction of hippocampal acetylcholine release is mediated by GABA(B) receptors and support a possible involvement of hippocampal GABA(B) receptors in the control of cognitive processes and in the claimed amnesic effect of GHB intoxication.

Acetylcholine↗
PubMed2001

Melatonin reduces anxiety induced by lipopolysaccharide in the rat.

In male Sprague-Dawley rats intraperitoneal (i.p.) injection of Escherichia coli lipopolysaccharide (0.25, 0.50 and 1 mg/kg) increased anxiety levels. This effect was reversed by a prior, concomitant, and subsequent i.p. treatment with melatonin (4 and 6 mg/kg). As the effects of melatonin upon the actions induced by lipopolysaccharide were reversed by the melatonin receptor antagonist luzindole (30 and 60 mg/kg, i.p.), we argued that they are, but not only, melatonin receptor mediated. These findings, in accordance with our previous works, suggest that melatonin could be useful in the treatment of sickness behaviour associated with systemic infection diseases or as adjuvant in the anti-anxiety therapy.

Animals↗
PubMed2001

Effects of chronic Delta(9)-tetrahydrocannabinol treatment on hippocampal extracellular acetylcholine concentration and alternation performance in the T-maze.

Delta(9)-Tetrahydrocannabinol (Delta(9)-THC), the psychoactive ingredient of cannabis sativa, reduces both extracellular hippocampal acetylcholine concentration and correct alternation tasks in the T-maze. The principal aim of this study was to determine whether a chronic Delta(9)-THC treatment would induce tolerance both to the reduction of extracellular hippocampal acetylcholine concentration and memory deficit produced by the drug. Our results show that a chronic Delta(9)-THC treatment (5mg/kg, i.p., twice daily for two weeks) did not produce tolerance to the inhibitory effects induced by the drug. Moreover, no strict temporal correlation between the two Delta(9)-THC effects was observed: the inhibition in extracellular acetylcholine concentration appeared only 80 min after treatment, while the reduction of correct alternation tasks in the T-maze began after 20 min. The cognitive and cholinergic effects induced by a chronic Delta(9)-THC treatment were completely blocked by the CB(1) cannabinoid receptor antagonist SR 141716A, indicating an involvement of CB(1) cannabinoid receptors in the persistent negative effects induced by the drug. These findings confirm the proposition that CB(1) cannabinoid receptors mediate the negative effects induced by Delta(9)-THC both on hippocampal extracellular acetylcholine concentration and correct alternation tasks in the T-maze, and they indicate that these effects may be differentiated. However, the major outcome of this work is the demonstration that no tolerance to the two inhibitory effects develops after a chronic Delta(9)-THC treatment.

Animals↗
PubMed2000

Elevated circulating levels of anandamide after administration of the transport inhibitor, AM404.

The biological actions of the endogenous cannabinoid anandamide are terminated by carrier-mediated transport into neurons and astrocytes, followed by enzymatic hydrolysis. Anandamide transport is inhibited by the compound N-(4-hydroxyphenyl)arachidonylamide (AM404). AM404 potentiates several responses elicited by administration of exogenous anandamide, suggesting that it may also protect endogenous anandamide from inactivation. To test this hypothesis, we studied the effects of AM404 on the plasma levels of anandamide using high-performance liquid chromatography/mass spectrometry (HPLC/MS). Systemic administration of AM404 (10 mg kg(-1) intraperitoneal, i.p. ) caused a gradual increase of anandamide in rat plasma, which was significantly different from untreated controls at 60 and 120 min after drug injection. In plasma, both AM404 and anandamide were associated with a plasma protein, which we identified as albumin by non-denaturing polyacrylamide gel electrophoresis. AM404 (10 mg kg(-1), i.p.) caused a time-dependent decrease of motor activity, which was reversed by the cannabinoid CB(1) receptor antagonist N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide.hydrochloride (SR141716A, 0.5 mg kg(-1), i.p). These results are consistent with the hypothesis that AM404 inhibits anandamide inactivation in vivo.

Amides↗
PubMed2000

Lipopolysaccharide increases arginine-vasopressin release from rat suprachiasmatic nucleus slice cultures.

The aim of this study was to determine whether Escherichia coli lipopolysaccharide at the doses of 25, 50 and 100 microM influences arginine-vasopressin (AVP) secretion in young rat suprachiasmatic nucleus (SCN) neurons. Lipopolysaccharide administered in the medium for 3 h increased significantly the arginine-vasopressin release lasting up to 6 h after treatment. These results provide the first evidence that lipopolysaccharide influences AVP secretion in SCN neurons. Moreover, these findings may explain some central effects observed in vivo after lipopolysaccharide administration.

Animals↗
PubMed2000

Permissive role of dopamine D(2) receptors in the hypothermia induced by delta(9)-tetrahydrocannabinol in rats.

Cannabinoids produce analgesia, hypomotility, catalepsy, cognitive deficits and positive reinforcement. Moreover, Delta(9)-tetrahydrocannabinol (9-THC) and synthetic cannabinoids stimulate dopaminergic neurons and increase dopamine release in different brain areas. In order to clarify the role of endogenously released dopamine in the hypothermic response to cannabinoids, the effect of D(1) and D(2) dopamine receptor agonists and antagonists on Delta(9)-THC-induced hypothermia was studied in rats. Delta(9)-THC (2.5 and 5 mg/kg intraperitoneally [IP]) decreased body temperature in a dose-related manner. This effect was antagonized not only as expected by the CB(1) cannabinoid receptor antagonist SR 141716A (0.5 mg/kg, IP) but also, unexpectedly, by the dopaminergic D(2) receptor antagonists S(-)-sulpiride (5 and 10 mg/kg, IP) and S(-)-raclopride (1 and 3 mg/kg, IP). Conversely, the hypothermic effect of Delta(9)-tetrahydrocannabinol was potentiated by the D(2) dopamine receptor agonists (-)-quinpirole (0.025 and 0.500 mg/kg, SC) and (+)-bromocriptine (0.5 and 1 mg/kg, IP). In contrast, the Delta(9)-THC-induced hypothermic effect was not modified by either by the D(1) dopamine agonist SKF 38393 (10 mg/kg SC) or by the D(1) dopamine antagonist SCH 23390 (0.5 mg/kg SC). These results suggest that the D(2) dopamine receptors have a permissive role in the hypothermic action of cannabinoids.

Animals↗
PubMed2000

Repeated lipopolysaccharide administration produces tolerance to anorexia and fever but not to inhibition of thirst in rat.

In 24 h water and food deprived rats, a single lipopolysaccharide treatment (0.25, 0.50 and 1 mg/kg, i.p.) induced inhibition of thirst and hunger as well as fever. Moreover, the same treatment increased serum cytokines, plasma nitrite/nitrate and corticosterone and urinary prostaglandin levels. In another group of 24 h water and food deprived rats, a repeated lipopolysaccharide treatment (0.25, 0. 50 and 1 mg/kg, i.p.), given at 0, 2, 6, 12 and 24 h, induced tolerance to inhibition of food intake and fever, but not to antidipsogenic effect. Moreover, the same repeated treatment stopped the increase in serum cytokines, plasma corticosterone and urinary prostaglandin concentrations and failed to reduce plasma nitrite/nitrate levels. This data, together with the evidence that a pretreatment with N(G)-nitro-L-arginine methyl ester hydrochloride (L-NAME) (5 and 10 microg per rat) reverses the antidipsogenic effects in lipopolysaccharide tolerant rats, suggests that the persistent reduction of water intake after a repeated lipopolysaccharide treatment is due to the antidipsogenic action of nitric oxide in the brain.

Animals↗
PubMed2000

D(2) dopamine receptors enable delta(9)-tetrahydrocannabinol induced memory impairment and reduction of hippocampal extracellular acetylcholine concentration.

1. The systemic administration of Delta(9)-tetrahydrocannabinol (2.5 - 7.5 mg kg(-1)) reduced hippocampal extracellular acetylcholine concentration and impaired working memory in rats. 2. Both effects were antagonized not only by the CB(1) cannabinoid receptor antagonist SR141716A (0.5 mg kg(-1), i.p.) but also unexpectedly by the D(2) dopamine receptor antagonist S(-)-sulpiride (5, 10 and 25 mg kg(-1), i.p.). Conversely, Delta(9)-tetrahydrocannabinol-induced memory impairment and inhibition of hippocampal extracellular acetylcholine concentration were potentiated by the subcutaneous administration of the D(2) dopamine receptor agonist (-)-quinpirole (25 and 500 microg kg(-1)). The inhibition of hippocampal extracellular acetylcholine concentration and working memory produced by the combination of (-)-quinpirole and Delta(9)-tetrahydrocannabinol was suppressed by either SR141716A or S(-)-sulpiride. 3. Our findings suggest that impairment of working memory and inhibition of hippocampal extracellular acetylcholine concentration are mediated by the concomitant activation of D(2) dopamine and CB(1) cannabinoid receptors, and that D(2) dopamine receptor antagonists may be useful in the treatment of the cognitive deficits induced by marijuana.

Acetylcholine↗
PubMed1999

Dopamine D(2) receptor antagonists prevent delta(9)-tetrahydrocannabinol-induced antinociception in rats.

Delta(9)-Tetrahydrocannabinol (1 and 5 mg/kg, i.p.) produced, dose-dependently, antinociceptive effects using hot plate and tail flick tests in rats. These effects were suppressed not only by the cannabinoid CB(1) receptor antagonist SR 141716A (0.5 mg/kg; i.p.) but also by the dopamine D(2) receptor antagonists S(-)-sulpiride (5 and 10 mg/kg; i.p.) and S(-)-raclopride (1.5 and 3 mg/kg; i.p.). Conversely, Delta(9)-tetrahydrocannabinol antinociceptive effects were potentiated by the dopamine D(2) receptor agonists (-)-quinpirole (0.025 mg/kg, s.c.) and (+)-bromocriptine (0.5 and 1 mg/kg; i.p.). Our results indicate that the antinociceptive effects of Delta(9)-tetrahydrocannabinol are mediated by the concomitant activation of cannabinoid CB(1) and dopamine D(2) receptors and that dopamine D(2) receptor agonists may be useful in improving the analgesic effects of cannabinoids.

Analgesics, Non-Narcotic↗
PubMed1999

Central effects of cromoglycate sodium salt in rats treated with lipopolysaccharide.

In 24-h water- and food-deprived rats, we have evaluated the effects of cromoglycate sodium salt, an inhibitor of the mast cell degranulation with anti-inflammatory and membrane-stabilizating activity, on the central effects induced by Escherichia coli lipopolysaccharide (LPS). Intraperitoneal (i.p.) injection of LPS (0.25, 0.50 and 1 mg/kg) induced a dose-dependent inhibition of water and food intake, fever, reduction in locomotor activity as well as increased anxiety levels. All these LPS effects were antagonized by a prior intracerebroventricular (i.c.v.) injection of cromoglycate sodium salt (100, 150 and 200 microg/rat). Our findings suggest that peripheral LPS administration may activate brain mast cells and indicate an involvement of these cells in brain pathophysiology.

Animals↗
PubMed1999

Synthesis, stability, and pharmacological evaluation of nipecotic acid prodrugs.

Nipecotic acid (1), one of the most potent in vitro inhibitors of neuronal and glial gamma-amino butyric acid (GABA) uptake, is inactive as an anticonvulsant when administered systemically. To obtain in vivo active prodrugs of (1), we synthesized four new nipecotic acid esters (3-6), which were obtained by chemical conjugation with glucose, galactose, and tyrosine. These compounds were assayed to evaluate their in vitro chemical and enzymatic hydrolysis. In addition, their anticonvulsant activity was evaluated in vivo in Diluted Brown Agouti (DBA)/2 mice, an excellent animal model for the study of new anticonvulsant drugs. Esters (3-6) appeared stable, at various temperatures, in a pH 7.4 buffered solution and showed susceptibility to undergoing in vitro enzymatic hydrolysis. Intraperitoneally injected nipecotic acid (1) and esters (3-5) did not protect mice against audiogenic seizures; conversely, nipecotic tyrosine ester (6) showed a significant dose-dependent anticonvulsant activity. The in vivo protective activity of the ester (6) and the inefficiency of nipecotic acid (1) in the same experimental conditions suggest that this ester prodrug could be actively transported intact across the blood-brain barrier, beyond which it could be hydrolyzed.

Animals↗
PubMed1998

Inhibition of hippocampal acetylcholine release after acute and repeated Delta9-tetrahydrocannabinol in rats.

The effects of acute and repeated administration of Delta9-tetrahydrocannabinol (Delta9-THC), the psychoactive principle of marijuana, on acetylcholine release in the hippocampus was studied in freely moving rats by microdialysis. The acute intraperitoneal (i.p.) administration of Delta9-THC at the doses of 2.5 and 5 mg/kg reduced acetylcholine release by about 25% and 45%, respectively. A dose of 7.5 mg/kg produced no further reduction. Delta9-THC effects were antagonized by the cannabinoid CB1 antagonist SR141716A at the i.p. dose of 1 mg/kg, per se ineffective in modifying acetylcholine concentrations. After a repeated exposure (twice daily for up to seven days) to Delta9-THC (7.5 mg/kg, i.p.) or vehicle (0.3 ml/kg, i.p.), the inhibitory effect of Delta9-THC (2.5 and 5 mg/kg, i.p) on acetylcholine release was not reduced. The results confirm previous observations that cannabinoids inhibit acetylcholine release through cannabinoid CB1 receptors, and indicate that no tolerance to this effects develops after a repeated Delta9-THC administration.

Acetylcholine↗
PubMed1998

Arrhythmogenic right ventricular dysplasia: pregnancy under flecainide treatment.

This is the first reported case of a young woman with a moderate to severe form of arrhythmogenic right ventricular dysplasia under flecainide treatment who, with her physician's consent, decided to have a baby. During the pregnancy, antiarrhythmic drug therapy was continued and plasma levels of flecainide were measured via high-performance liquid chromatography. Every three months, she was monitored by means of resting ECG, signal-averaging ECG, 24-hour ECG and echocardiogram. We did not observe any meaningful events. A normal baby was delivered at full term by cesarean section. The baby's Apgar score was 9 after 1 and 5 minutes. The baby had to be fed using artificial milk. In conclusion, no changes in the pathology of the right ventricle were observed, we did not record any arrhythmia and the use of flecainide acetate did not cause any teratogenic effects. Nevertheless, we cannot assign any epidemiologic value to our report.

Adult↗
PubMed1997

Melatonin effects on inhibition of thirst and fever induced by lipopolysaccharide in rat.

In 24 h water deprived rats we have evaluated the effects of melatonin on the inhibition of thirst and on fever induced by Escherichia coli lipopolysaccharide. Intraperitoneal (i.p) injection of lipopolysaccharide (0.32, 0.64 and 0.96 mg/kg) alone induced, a dose-dependent and significant inhibition of water intake as well as fever. In addition, lipopolysaccharide at the same concentrations increased urinary prostaglandins and serum cytokines levels. On the contrary, lipopolysaccharide treatment had no effects on cerebral brain nitric oxide synthase activity. All lipopolysaccharide effects were reverted by a prior, concomitant and subsequent i.p. treatment with melatonin (2, 4 and 6 mg/kg), whereas they were still present when melatonin was injected in combination with the melatonin receptor antagonist luzindole (15, 30 and 60 mg/kg, i.p.). We suggest that melatonin could exert its dipsogenic effects through a reduction of the free radical nitric oxide (NO.) whereas it may reduce body temperature by preventing an excessive formation of prostaglandins and cytokines.

Animals↗
PubMed1997

Convulsant effects of some xanthine derivatives in genetically epilepsy-prone rats.

The behavioural and electrocorticographic (ECoG) convulsant effects of several xanthine derivatives injected intraperitoneally (i.p.) were studied in genetically-epilepsy prone rats. The aim of the study was to evaluate the relationship among convulsant potency, molecular structure and lipophilicity of some xanthines. Animals were injected i.p. with various doses (250-1000 micromol/kg) and a different convulsant potency was observed among the various xanthines tested. IBMX (3-isobutyl-1-methylxanthine), theophylline (1,3-dimethylxanthine) and caffeine (1,3,7-trimethylxanthine) induced an epileptogenic pattern that consisted in an initial phase characterized by wet-dog shakes followed by head tremor, nodding, clonic convulsion and they appeared to be the most potent xanthines among those studied. During seizures, the electrocortical activity was usually characterized by single or multiple sharp- or spike-wave episodes followed by polyspike discharges. After the highest doses of IBMX, theophylline and caffeine, the animals react with falling down, transient tonic clonic seizures, escape response and generalized seizures followed by post-ictal period. Equimolar doses of 8-chlorotheophylline and theobromine (3,7-dimethylxanthine) produced less evident epileptic responses in comparison to previous compounds, whereas no epileptic signs were observed following the administration of enprofylline (3-propylxanthine), etofylline [7-(2-hydroxyethyl)theophylline], diprophylline [7-(2,3-dihydroxy-propyl)theophylline] and doxofylline [7-(1,3-dioxolan-2-ylmethyl) theophylline]. Lipophylicity of the compounds was determined, but no convincing correlations were found between the rank order of lipophilicities and the convulsant potencies of the compounds studied. On the other hand, structure-activity relationship was also investigated. We suggest that the substitution pattern on the xanthine nucleus may explain, in part, the different convulsant potency of the compounds studied. Furthermore, a selective antagonism of adenosine subtype receptors should be considered.

1-Methyl-3-isobutylxanthine↗
PubMed1997

Zymosan-activated plasma induces paw oedema by nitric oxide and prostaglandin production.

Injection of zymosan-activated plasma into the rat paw induced oedema formation. Subplantar injection of the non isoform- selective inhibitors of nitric oxide (NO) synthase, N(G)-nitro-L-Arginine methyl ester and N(G)-methyl-L-Arginine, and of a scavenger of NO, haemoglobin, inhibited the early phase of oedema development. Inhibition of cyclooxygenase activity by indomethacin reduced the late increase in paw volume after the injection of zymosan-activated plasma. Methylene blue, an inhibitor of the soluble guanylate cyclase, had no effect. Our results suggest that in paw oedema induced by zymosan-activated plasma, the inflammatory response is dependent on NO (for the early phase) and prostaglandins (for the late phase). The effect of NO is likely to be mediated by a pathway which does not involve cyclic GMP.

Animals↗