Neurobehavioral effects of chronic low-dose risperidone administration in juvenile male rats

Abstract

Despite substantial increases in the use of antipsychotics to treat various psychiatric conditions in children, there is a lack of literature regarding long-term effects of early treatment. Some studies have indicated that early administration results in differential alterations to neurotransmission systems, but few studies have investigated whether there are long-term behavioral modifications. Therefore, the aim of the current study was to investigate the neurobehavioral effects of low dose risperidone (a commonly prescribed antipsychotic) treatment using juvenile rats. Twenty-four male Sprague-Dawley rats were either subcutaneously implanted with a continuous release risperidone pellet (.04 mg/day) or a placebo pellet. To encompass the peri-adolescent to adolescent timeframe (postnatal day 40–70) thought to be important for brain development, male rats began risperidone treatment at post-natal day 35. Six weeks following commencement of risperidone treatment, all rats were tested on a battery of behavioral assessments including open field, object recognition, Morris Water Maze, and Y-Maze tasks. Risperidone treatment did not affect performance on the open field, object recognition, or Morris Water maze. A significant effect was found on the Y-maze. Although all rats exhibited normal spontaneous alternation, risperidone treated rats demonstrated significantly higher same arm returns, indicative of a working memory deficit. Continued research is needed to determine whether early exposure to risperidone may lead to differences in working memory at longer time-points. These results seem to indicate that early low dose risperidone treatment during the peri-adolescent and adolescent period does not severely impair behavior.