RESUMO
Although many studies have investigated the function of cellular prion protein (PrPc), its physiologic role remains elusive. PrPc null mice have been reported to develop normally and to show normal performance in most behavioural tests. In the present study we investigated whether this also holds true after episodes of acute stress. PrPc gene ablated (Prnp0/0) and wild-type mice were subjected to restraint stress, electric foot shock, or swimming and compared with non-stressed animals. Immediately after the stressful situation, the anxiety levels and locomotion of the animals were measured using plus-maze and open-field tests. Among non-stressed animals, there was no significant difference in performance between Prnp0/0 and wild type animals in either test. However, after acute stress provoked by a foot shock or a swimming trial, Prnp0/0 animals showed a significant decrease in anxiety levels when compared with control animals. Moreover, after the swimming test, knockout mice presented decreased locomotion when compared to wild-type mice. Because of this observation, we also assessed both types of mice in a forced swimming test with the objective of better evaluating muscle function and found that Prnp0/0 animals presented reduced forced swimming capacity when compared to controls. As far as we know, this is the first report suggesting that cellular prion protein is involved in modulation of anxiety or muscular activity after acute psychic or physical stress.
Assuntos
Comportamento Animal/fisiologia , Proteínas PrPC/deficiência , Estresse Psicológico/genética , Estresse Psicológico/fisiopatologia , Análise de Variância , Animais , Eletrochoque/métodos , Comportamento Exploratório/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Tempo de Reação/efeitos da radiação , Restrição Física/métodos , Natação/fisiologiaRESUMO
Acute administration of intraperitoneal and oral guanosine has been shown to prevent quinolinic acid and alpha-dendrotoxin-induced seizures in rats and mice. In this study, we investigated the effects of 2 weeks ad libitum consumption of guanosine (0.5 mg/ml) added to mice water supply on seizures and lethality induced by the alpha-dendrotoxin, hole-board behavior, inhibitory avoidance task, locomotor activity, motor coordination, rectal temperature, body weight, and water and food consumption. Guanosine prevented seizures in 40% and death in 50% on mice treated with i.c.v. alpha-dendrotoxin; it also impaired inhibitory avoidance memory and increased head-dipping behavior and locomotor activity on the hole-board test. Guanosine consumption did not alter any of the other parameters evaluated. The anticonvulsant, amnesic, and anxyolytic-like effects may be associated with the ability of guanosine in modulating the glutamatergic excitatory system. Adding to previously reported data, these findings suggest a potential role for chronic guanosine in the management of diseases associated with glutamatergic excitotoxicity, including epilepsy and anxiety.
Assuntos
Anticonvulsivantes/uso terapêutico , Guanosina/uso terapêutico , Convulsões/prevenção & controle , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/uso terapêutico , Anticonvulsivantes/administração & dosagem , Ansiedade/prevenção & controle , Comportamento Animal/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Vias de Administração de Medicamentos , Esquema de Medicação , Venenos Elapídicos/toxicidade , Comportamento Exploratório/efeitos dos fármacos , Guanosina/administração & dosagem , Masculino , Camundongos , Atividade Motora/efeitos dos fármacos , Neurotoxinas , Tempo de Reação/efeitos dos fármacos , Convulsões/induzido quimicamente , Convulsões/mortalidadeRESUMO
Extracellular guanine-based purines, mainly the nucleoside guanosine, have recently been shown to exert neuroprotective effects, which seem to be related to antagonism of the glutamatergic system. In this study, we investigated the effects of acute oral administration of guanosine on inhibitory avoidance task in rats and mice. We also studied its effects on locomotor activity, anxiety-related behaviors and mechanisms of action involving the purinergic system. Guanosine (2.0 and 7.5mg/kg, per os), administered 75min pretraining, dose-dependently impaired retention of the inhibitory avoidance task in rats and mice, an effect not prevented by the adenosine receptor antagonist caffeine. Guanosine presented no effects on locomotor activity and anxiety-related behaviors. This amnesic effect of guanosine may be compatible with inhibition of glutamatergic system and seems to be not mediated by adenosine.