BEHAVIORAL-EFFECTS OF GM1 GANGLIOSIDE TREATMENT AND INTRAHIPPOCAMPAL SEPTAL GRAFTS IN RATS WITH FIMBRIA-FORNIX LESIONS

The monosialoganglioside GM1 is a compound with neurotrophic propertie s found to foster functional recovery in various paradigms of brain da mage. The present experiment examined whether systemic treatment with GM1 may facilitate behavioral recovery in rats with fimbria-fornix les ions and intrahippocampal grafts rich in cholinergic neurons. Among 68 Long-Evans female rats, 46 sustained a bilateral electrolytic lesion of the fimbria and the dorsal fornix and 22 were sham-operated, Fourte en days later, half the lesioned rats were subjected to intrahippocamp al grafts of a fetal septal cell suspension. Starting a few hours afte r lesion surgery and over a 2-month period, half the rats of each surg ical treatment group received a daily injection of GM1 (30 mg/kg i.p.) , the other half being injected with saline as a control. All rats wer e subsequently tested for locomotor activity and radial maze learning. The lesions induced locomotor hyperactivity and impaired learning per formances in both an uninterrupted and an interrupted radial maze test ing procedure. In all rats with surviving grafts, the grafts had provi ded the hippocampus with a new and dense organotypic acetylcholinester ase-positive innervation pattern which did not differ between saline- and GM1-treated subjects. The scores/performances of the rats that had received only the grafts or only the GM1 treatment did not differ sig nificantly from those of their respective lesion-only counterparts, Ho wever, in the radial-arm maze task, the grafted rats given GM1 showed improved learning performances as compared with their saline-treated c ounterparts: they used more efficient visit patterns under the uninter rupted testing conditions and made fewer errors under the inter disrup ted ones. The results suggest that GM1 treatment or intrahippocampal g rafts used separately do not attenuate the lesion-induced behavioral d eficits measured in this experiment. However, when GM1 treatment and g rafts are used conjointly, both may interact in a manner allowing part of these deficits to be attenuated.