The effects of a specific alpha(2)-adrenoceptor antagonist, atipamezole, on cognitive performance and brain neurochemistry in aged Fisher 344 rats

The present experiments investigated the effects of a specific and potent alpha(2)-adrenoceptor antagonist, atipamezole, on cognitive performance and neurochemistry in aged rats. Aged control Fisher 344 rats, which had lower activities of choline acetyltransferase in the frontal cortex, were impaired in the acquisition of the linear arm maze task both in terms of repetition errors and their behavioural activity (the speed of arm visits), and they needed longer time to complete this task as compared to adult control rats. Atipamezole treatment (0.3 mg/kg) facilitated the acquisition of this task in the aged rats as they committed fewer errors and completed the task more quickly than saline-treated aged control rats. A separate experiment indicated that atipamezole enhanced the turnover of noradrenaline both in the adult and aged rats, but this effect was more pronounced in the aged rats. Furthermore, atipamezole enhanced significantly the turnover of serotonin and dopamine only in the aged rats when analysed in the whole brain samples. As alpha(2)-adrenoceptor antagonists are known to alleviate akinesia in the experimental models of Parkinson's disease, the present results could be especially relevant for the development of palliative treatment for demented Parkinsonian patients.