RESUMEN
OBJECTIVE AND DESIGN: To characterize the effects of swim stress on the early mast cell (MC)-dependent peritoneal production of TNF in response to lipopolysaccharide (LPS) administration in mice, identifying the neuroendocrine mediators involved. SUBJECTS: Ten to twelve-week-old Swiss Webster, C57BL/6 J or c-Kit (Wsh/Wsh) mice were used. TREATMENT: Animals were intraperitoneally challenged with LPS at different times after forced swimming (FS) and peak TNF production was determined in peritoneal washes at optimal time after LPS administration. Selective blockage of main neuroendocrine pathways was performed before swim stress. METHODS: TNF concentrations were determined by ELISA. RESULTS: FS provoked an immediate and transient inhibition of LPS-elicited, MC-dependent TNF accumulation in peritoneum, which lasted around 30 min. Suppresive effects of FS were absent on MC-deficient c-Kit (Wsh/Wsh) mice but were recovered after reconstitution with MC. Adrenalectomy or DSP4 administration increased basal ip TNF levels and enhanced LPS-induced TNF release without any effect on stress-induced inhibitory effects, mifepristone did not produce any change on stress-induced inhibition, whereas mecamylamine administration increased basals and attenuated stress effects. CONCLUSIONS: Swim stress transiently inhibits the canonical MC-dependent response of TNF production in response to LPS in murine peritoneal cavity with the main participation of the cholinergic anti-inflammatory reflex.
Asunto(s)
Mastocitos/inmunología , Peritoneo/inmunología , Estrés Fisiológico/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Glándulas Suprarrenales/inmunología , Animales , Lipopolisacáridos , Ratones Endogámicos C57BL , Ratones Transgénicos , Proteínas Proto-Oncogénicas c-kit/genética , NataciónRESUMEN
Toluene is a volatile organic solvent with addictive potential that exhibits similarities in its physiological effects and modes of action to other addictive drugs. Despite its widespread abuse, the molecular mechanisms driving the response and adaptation of the organism to this drug are not fully understood. In recent years, different epigenetic mechanisms that modulate gene expression have been shown to be associated to cocaine, amphetamine and alcohol misuse-induced alterations in neuronal function. For example, it has been demonstrated that drug consumption induces variations in histone acetylation levels in brain reward regions and these play a relevant role on the abuse-associated behavioral plasticity. In order to decipher whether repeated toluene exposure could mediate epigenetic changes in the rat brain, we here analyzed the acetylation pattern of histones H3 and H4 in three brain areas that have been previously associated to substance abuse reward pathways: the Nucleus Accumbens (NAc), the Ventral Tegmental Area (VTA) and the Central Amygdala (CeA). Using immunofluorescence analysis of brain sections with specific antibodies that recognize the acetylated forms of histones H3 and H4, we demonstrate that chronic toluene inhalation differentially modifies histone H3 and H4 acetylation in the NAc and the VTA while no effect is observed in the CeA. Our results suggest that the activity of chromatin-modifying enzymes such as histone de-acetylases (HDACs) in certain brain areas are responsive to toluene inhalation and might be crucial mediators in the addictive response to toluene.
Asunto(s)
Amígdala del Cerebelo/efectos de los fármacos , Histona Acetiltransferasas/metabolismo , Histona Desacetilasas/metabolismo , Histonas/metabolismo , Núcleo Accumbens/efectos de los fármacos , Tolueno/toxicidad , Área Tegmental Ventral/efectos de los fármacos , Acetilación/efectos de los fármacos , Administración por Inhalación , Amígdala del Cerebelo/enzimología , Animales , Epigénesis Genética/efectos de los fármacos , Masculino , Núcleo Accumbens/enzimología , Ratas , Ratas Wistar , Tolueno/administración & dosificación , Área Tegmental Ventral/enzimologíaRESUMEN
Toluene is an abused solvent widely used in several commercial products. Recent evidence indicates that this solvent is a non-competitive inhibitor of NMDA receptors. Since NMDA receptors have been implicated in pain, this paper describes studies of the effects of increasing concentrations of inhaled toluene on nociception. Swiss Webster mice were exposed to toluene (500-8000 ppm) in static exposure chambers for 30 min. After completing the exposure period, animals were tested for nociception using the hot plate test. Toluene dose-dependently increased nociception as reflected by shorter latencies for the reflex, paw-lick and escape responses in toluene-treated mice with respect to their controls (animals exposed to air). In order to determine the possible role of opioids in this response, morphine (1-10 mg/kg) was injected before toluene inhalation. Toluene was not able to block morphine-induced antinocieption, however, it produced a shift of the morphine dose-response curve to lower effects, suggesting a physiological antagonism. No potentiation was seen when toluene was administered in combination with naloxone. Present results suggest that toluene increases nociception via neurotransmitter systems others than the glutamatergic.
Asunto(s)
Nociceptores/efectos de los fármacos , Dimensión del Dolor/efectos de los fármacos , Tolueno/farmacología , Administración por Inhalación , Analgésicos Opioides/farmacología , Animales , Conducta Animal/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Calor , Masculino , Ratones , Morfina/farmacología , Equilibrio Postural/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Tolueno/administración & dosificaciónRESUMEN
This paper compares the anxiolytic-like actions of toluene in two anxiety paradigms, the burying behavior and plus-maze tests, in 5-HT(1B) knockout (KO) and 129/Sv-ter wild-type (WT) mice. Static exposures were conducted in 29-l gas chromatographic jars. Animals were exposed to toluene (0, 1000, 2000 or 4000 ppm; n=8-12, each) for 30 min, and immediately after, tested in one of the anxiety paradigms. Motor coordination was evaluated in the rota-rod test in independent groups of mice. Toluene produced a dose-dependent decrease in anxiety-like levels in both anxiety paradigms and in both the strains. However, toluene exerted its effects at lower concentrations in KO mice than in the WT strain. These results cannot be attributed to a decrease in motor coordination since all the animals behaved similarly in the rota-rod test, regardless of the treatment. To discard any inherent difference in the nociception threshold between strains, mice were tested in the hot plate immediately after being exposed to either air or toluene. Toluene increased nociception in a similar fashion in both the strains. Our results suggest that 5-HT(1B) KO mice are more sensitive to those of toluene's actions related to anxiety, but not to those related with motor coordination or nociception. Data are discussed in terms of toluene's mechanisms of action and on differences between WT and KO animals.
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Ansiolíticos/farmacología , Ansiedad/psicología , Conducta Animal/efectos de los fármacos , Receptores de Serotonina/fisiología , Tolueno/farmacología , Animales , Cromatografía Líquida de Alta Presión , Masculino , Ratones , Ratones Noqueados , Dimensión del Dolor/efectos de los fármacos , Equilibrio Postural/efectos de los fármacos , Tiempo de Reacción/efectos de los fármacos , Receptor de Serotonina 5-HT1B , Receptores de Serotonina/genéticaRESUMEN
Putative gender differences in opiate cardiovascular effects were evaluated in spinal rats. After a 4-h exposure to a single dose of morphine (30 mg/kg, i.v.), abstinence was precipitated by naloxone (0.03-3 mg/kg, i.v.). Morphine produced a long-lasting bradycardia and a transient increase in arterial pressure that was similar in both genders. Thereafter, blood pressure decreased both in males and females. Naloxone precipitated a similar dose-dependent heart rate increase in both sexes and a gender-dependent increase in blood pressure. This sex difference appeared in the shape of the response. Prazosin (0.2 mg/kg), prior to naloxone, reduced the pressor response in all animals, suggesting a similar participation of the noradrenergic system in both genders. The present results extend to acute dependence the notion of a sex-dependent differential effect of morphine. The need to consider gender as a factor when studying the effects of opioids is highlighted.
Asunto(s)
Analgésicos Opioides/farmacología , Sistema Cardiovascular/efectos de los fármacos , Morfina/farmacología , Naloxona/farmacología , Antagonistas de Narcóticos/farmacología , Médula Espinal/efectos de los fármacos , Antagonistas Adrenérgicos alfa/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Sistema Cardiovascular/fisiopatología , Relación Dosis-Respuesta a Droga , Femenino , Frecuencia Cardíaca/efectos de los fármacos , Masculino , Dependencia de Morfina/fisiopatología , Prazosina/farmacología , Ratas , Ratas Wistar , Factores Sexuales , Médula Espinal/patologíaRESUMEN
The effect of the 5-HT1A agonists ipsapirone (5 mg/kg), buspirone (5 mg/kg) and 8-OH-DPAT (0.5 mg/kg) on experimental anxiety was examined in sham-operated, adrenalectomized and adrenally demedullated male rats. The animal model of anxiety used was the defensive burying test. At the doses selected, all 5-HT1A compounds produced an anxiolytic-like action by reducing the burying behavior in both sham-operated and demedullated rats. However, in adrenalectomized subjects, while 8-OH-DPAT still reduced burying behavior, ipsapirone and buspirone lost their action. Data suggest that adrenocortical secretions play a role in the anxiolytic-like actions of buspirone and ipsapirone, but not in those of 8-OH-DPAT. Buspirone and ipsapirone also produced a reduction in burying behavior latency in sham-operated animals that was not observed in adrenalectomized or adrenally demedullated rats. These data suggest that adrenaline may be participating in the action of these compounds on the burying behavior latency. Present findings support possible direct relationships between the stimulation of 5-HT1A receptors and adrenal secretions.
Asunto(s)
8-Hidroxi-2-(di-n-propilamino)tetralin/farmacología , Adrenalectomía , Ansiolíticos/farmacología , Buspirona/farmacología , Pirimidinas/farmacología , Médula Suprarrenal/cirugía , Animales , Conducta Animal/efectos de los fármacos , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas Wistar , Serotoninérgicos/farmacologíaRESUMEN
Sixteen patients acutely poisoned with aldrin were examined to evaluate a possible correlation between serum aldrin and diedrin levels and clinical complaints. The patients were classified as having mild (N = 8), moderate (N = 5) or severe (N = 3) poisoning according to clinical symptoms. Concentrations of less than 20 µg/l were usually associated with mild poisoning, which involved complaints such as nausea, vomiting and epigastric pain, whereas concentrations of 100 to 200 µg/l were considered to represent moderate intoxication and were associated with nausea, vomiting, epigastric pain, headache, dizziness, and convulsions. Sever or fatal cases were associated with levels above 700 µg/l. Taken together,these results suggest that serum aldrin diedrin levels can be used as indicators of clinical prognosis after acute poisoning with these insecticides and that convulsions could suddenly occur even in the absence of prodronal signs or symptoms
Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Adolescente , Adulto , Aldrín/envenenamiento , Dieldrín/envenenamiento , Enfermedad Aguda , Aldrín/sangre , Cromatografía de Gases , Convulsiones/inducido químicamente , Dieldrín/sangreRESUMEN
Sixteen patients acutely poisoned with aldrin were examined to evaluate a possible correlation between serum aldrin and dieldrin levels and clinical complaints. The patients were classified as having mild (N = 8), moderate (N = 5) or severe (N = 3) poisoning according to clinical symptoms. Concentrations of less than 20 micrograms/l were usually associated with mild poisoning, which involved complaints such as nausea, vomiting and epigastric pain, whereas concentrations of 100 to 200 micrograms/l were considered to represent moderate intoxication and were associated with nausea, vomiting, epigastric pain, headache, dizziness, and convulsions. Severe or fatal cases were associated with levels above 700 micrograms/l. Taken together, these results suggest that serum aldrin and dieldrin levels can be used as indicators of clinical prognosis after acute poisoning with these insecticides and that convulsions could suddenly occur even in the absence of prodromal signs or symptoms.
Asunto(s)
Aldrín/envenenamiento , Dieldrín/envenenamiento , Enfermedad Aguda , Adolescente , Adulto , Aldrín/sangre , Preescolar , Cromatografía de Gases , Dieldrín/sangre , Femenino , Humanos , Lactante , Masculino , Pronóstico , Convulsiones/inducido químicamenteRESUMEN
In the attempt to correlate clinical findings with serum levels of aldrin, sixteen patients were followed-up after acute intoxication by this agent. Eight of them, males and females, aged from 1 to 37 years, presented no or light symptoms (some discomfort and nausea). The serum of one of these patients was found to contain 16.6 ppb of aldrin and that of another, 1.41 ppb of dieldrin. A group of five patients, aged from two to 30 years, showed symptoms of moderate severity, reporting nausea, vomiting, drowsiness, dyspnea, sweating, mild jerking, rise in blood pressure and convulsions. Of these cases, two were accidental and three were attempted suicides, the majority achieving complete recovery within 24 hours. Serum levels of aldrin were between 6.98 ppb and 26.3 ppb and of dieldrin between 82.00 and 314.18 ppb. We found three severe cases, aged from 21 to 35 years, two attempted suicides and one occupational case. Two of these patients died and one of them presented hypothermia, coma, absence of reflexes and generalized convulsions, and another presented abdominal pain, paleness, sweating, cold extremities, dyspnea, hyperthermia and generalized convulsions. In the first one that died the serum levels were: of aldrin 30.00 ppb and of dieldrin 720 ppb. In the other levels of 747.3 ppb of aldrin and 1,314.00 ppb of dieldrin were found. The third had less serious symptoms and presented serum levels of aldrin of 31.05 ppb and of dieldrin 147.11 ppb.(ABSTRACT TRUNCATED AT 250 WORDS)