Psychotropic Medication and Functional Recovery following Cortical Stroke in Aged Rats

Recovery process following cerebral insults such as stroke is affected by aging and can be modulated by pharmacotherapy. The purpose of this series of studies was to evaluate the effect of new psychotropic medications on the histological and functional outcome following cortical stroke in aged rats which might be more vulnerable to brain insults. This follows clinical practice in which elderly patients who are taking psychotropic medication sustain small focal strokes. We evaluated the effects of galanthamine, a selective competitive cholinesterase inhibitor, risperidone, an atypical neuroleptic, alone or in combination with fluoxetine, a selective serotonin reuptake inhibitor, and zopiclone, a hypnotic drug. Acute and chronic drug effects or the effects after a washout period on sensorimotor performance and spatial learning were studied by a novel tapered beam-walking task and match-to-place version of the Morris water-maze test, respectively. The main results were: 1) galanthamine is not beneficial or harmful with respect to the histological or functional outcome in young or aged rats subjected to cortical photothrombosis, 2) risperidone does not affect histological or long-term functional outcome in aged rats subjected to cortical photothrombosis, but its extrapyramidal side effects are likely to acutely impair behavioral performance, 3) fluoxetine alone or in combination with risperidone did not affect histological or behavioral outcome, and 4) long-term administration of zopiclone, did not worsen functional outcome, and even slightly improved behavioral performance following cortical infarct in aged rats. Taken together, the present data demonstrate that aged rats can undergo a remarkable functional recovery after being subjected to cortical stroke. New psychotropic drugs used commonly in the elderly seem to be relatively safe with respect to sensorimotor and cognitive recovery once the treatment was discontinued. Infarct volumes were not affected by the studied drugs. National Library of Medicine Classification: WL 355, QY 60.R6 Medical Subject Headings: aging; aged; ischemic attack; drug therapy; recovery of function; neuronal plasticity; animals; rats To my wife, Mei Zhao