Quinolinic acid (QUIN) is a neuroactive metabolite of the kinurenine pathway, and is considered to be involved in aging and some neurodegenerative disorders, including Huntington's disease. QUIN was injected intrastriatally into adolescent rats, and biochemical and histopathological analyses in the striatum, cortex, and hippocampus, as well as behavioral tests, were carried out in the rats over a period of 21 days after drug injection. Decreased 3Hglutamate uptake and increased 45Ca2+ uptake were detected shortly after injection in the striatum and cerebral cortex. In the hippocampus, increased 45Ca2+ uptake preceded the decreased 3Hglutamate uptake, without histopathological alterations. Also, corticostriatal astrogliosis was observed 7 days later, progressing to neuronal death at day 14. QUIN‐treated rats also showed cognitive deficits 24 h after injection, concurrently with striatal astrogliosis. Motor deficits appeared later, after corticostriatal neurodegeneration. We assume that glutamate excitotoxicity could represent, at least in part, a molecular mechanism associated with the cognitive and motor impairments, corticostriatal astrogliosis and neuronal death observed in the QUIN‐treated rats. We propose that our findings could be relevant for understanding the pathophysiology of human neurodegenerative diseases affecting young people, such as the juvenile form of Huntington's disease, and for the design of potential therapeutic strategies to slow down the progression of the disease. Quinolinic acid intrastriatally injected in adolescent rats produced a short‐term decrease in 3H‐glutamate uptake and increase in 45Ca2+ uptake in the striatum, cerebral cortex and hippocampus, accompanied by striatal astrogliosis and cognitive deficits. Corticostriatal astrogliosis was a later event, progressing to neuronal death, while no histopathological changes were observed in the hippocampus. Motor deficits appeared later, after corticostriatal neurodegeneration.