RESUMO
Previous studies have demonstrated that zymosan, a cell wall component of the yeast Saccharomyces cerevisiae, induces inflammation in experimental models. However, few studies have evaluated the potential of zymosan to induce sickness behavior, a central motivational state that allows an organism to cope with infection. To determine whether zymosan administration results in sickness behavior, mice were submitted to the forced swim (FST) and open field (OFT) tests 2, 6, and 24 h after treatment with zymosan (1, 10, or 100 mg/kg). Additionally, to evaluate the possible relationship between zymosan-induced sickness behavior and prostaglandin synthesis, mice were pretreated with the cyclooxygenase inhibitors indomethacin (10 mg/kg) and nimesulide (5 mg/kg) and the glucocorticoid drug dexamethasone (1 mg/kg). Zymosan induced time-dependent decreases in locomotor activity in the OFT, and an increase in immobility in the FST, and increased plasma levels of corticosterone at 2 h. Pretreatment with indomethacin, nimesulide, or dexamethasone blocked zymosan-induced behavioral changes in both the FST and OFT at 2 h post administration. These findings confirm previous observations that zymosan induces sickness behavior. Furthermore, our results provide new evidence that prostaglandin synthesis is necessary for this effect, as anti-inflammatory drugs that inhibit prostaglandin synthesis attenuated zymosan-induced behavioral changes.
Assuntos
Comportamento de Doença/efeitos dos fármacos , Indometacina/farmacologia , Antagonistas de Prostaglandina/administração & dosagem , Prostaglandinas/metabolismo , Sulfonamidas/farmacologia , Zimosan/toxicidade , Animais , Comportamento Animal/efeitos dos fármacos , Dexametasona/farmacologia , Relação Dose-Resposta a Droga , Glucocorticoides/administração & dosagem , Glucocorticoides/farmacologia , Indometacina/administração & dosagem , Masculino , Camundongos , Zimosan/administração & dosagemRESUMO
Arteriovenous anastomoses disrupt cardiovascular and renal homeostasis, eliciting hemodynamic adjustments, resetting the humoral pattern, and inducing cardiac hypertrophy. Because acute circulatory imbalance alters gut motor behavior, we studied the effects of arteriovenous fistula placement on the gastric emptying (GE) of a liquid meal in awake rats. After laparotomy, we created an aortocaval fistula (ACF) by aorta and cava wall puncture with a 21-, 23-, or 26-gauge needle. The ACF was not created in the control group, which underwent sham operation. After 12, 24, or 48 h, mean arterial pressure, heart rate, and central venous pressure were continuously recorded, and cardiac output was estimated by thermal dilution. The rats were then gavage fed a test meal (i.e., phenol red in glucose solution), and fractional dye retention was determined 10, 20, or 30 min later. The effect of prior bleeding on ACF-induced GE delay, the role of neuroautonomic pathways, and changes in plasma hormone levels (i.e., angiotensin II, arginine vasopressin, atrial natriuretic peptide, corticosterone, and oxytocin) were evaluated. When compared with the sham-operated group, ACF rats exhibited arterial hypotension, higher (P < 0.05) heart rate, central venous pressure, and cardiac output values and increased (P < 0.05) gastric dye retention, a phenomenon prevented by bilateral subdiaphragmatic vagotomy and hexamethonium treatment. Pirenzepine also impaired the occurrence of gastric delay in subjects with ACF. In addition to causing hyperkinetic circulation, ACF placement delayed the GE of liquid in awake rats, an effect that likely involves a parasympathetic pathway.