RESUMO
The unexpected discovery that certain chemotherapeutic agents used in the treatment of childhood cancers have neurocognitive side effects has prompted a search for techniques that identify those medications that place children at risk. An animal model for the assessment of resultant neurocognitive toxicity is described which makes use of simple classical conditioning. We have shown that rats learn about environmental events more slowly following neonatal administration of methotrexate. The changes after methotrexate exposure are not related to stimulus characteristics or to perceptual abilities, but rather to damage to the neural systems involved in acquisition, retention, or recall. Similar problems with learning have been observed in children treated with methotrexate. An effective animal model such as the one described here may help detect and avoid antineoplastic agents that produce severe cognitive defects in childhood cancer patients.
Assuntos
Cognição/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Metotrexato/toxicidade , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Encéfalo/anatomia & histologia , Encéfalo/efeitos dos fármacos , Condicionamento Clássico/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Masculino , Ratos , Ratos Endogâmicos Lew , PaladarAssuntos
Coriocarcinoma/fisiopatologia , Mola Hidatiforme Invasiva/fisiopatologia , Mola Hidatiforme/fisiopatologia , Antineoplásicos/uso terapêutico , Coriocarcinoma/tratamento farmacológico , Coriocarcinoma/patologia , Feminino , Humanos , Mola Hidatiforme/tratamento farmacológico , Mola Hidatiforme/patologia , Mola Hidatiforme Invasiva/tratamento farmacológico , Mola Hidatiforme Invasiva/patologia , GravidezRESUMO
Learning deficits have been noted in children with acute leukemia given methotrexate (MTX) with and without cranial irradiation (RT) for prophylaxis. A rat model has been developed to assess treatment effects on learning. The test used was altered performance of a simultaneous discrimination task in a standard operant conditioning box, employing the mean number of days needed to score 80% correct responses as the criterion. An illustrative experiment distributed suckling rats among four groups: (1) 36 controls; (2) 14 cranial RT (1,000 R); (3) 14 MTX (5 mg/kg i.p.); (4) 36 RT + MTX 24 h later, and (5) 12 undernourished controls (to match poor weight gain patterns of treated animals). Survivors were tested 10-12 weeks later: values for groups 1-5 in order were 3.9, 4.1, 4.7, 5.0 and 4.0 days. Only group 4 results were significantly different from group 1 (p = less than 0.05).