COMPARISON OF INTRACRANIAL INFUSIONS OF COLCHICINE AND IBOTENIC ACID AS MODELS OF NEURODEGENERATION IN THE BASAL FOREBRAIN

Colchicine and ibotenic acid were compared for their ability to produc e neurodegeneration and cognitive deficit after bilateral infusions in to the nucleus basalis magnocellularis of male Long-Evans rats. Four w eeks post-lesion, there was no difference in locomotor activity follow ing infusion of either neurotoxicant or vehicle. In a passive avoidanc e task, both treated groups had significantly shorter step-through lat encies compared with vehicle. Five weeks post-lesion, rats were killed for neurochemistry or histochemistry. Choline acetyltransferase (ChAT ) activity in both the frontal and parietal cortex was significantly d ecreased (25-35%) in the colchicine- and ibotenic acid-infused rats wh en compared to control. There was no effect of either neurotoxicant on ChAT activity in the hippocampus or striatum. Both neurotoxicants pro duced damage in the general area of the ventromedial pallidum, althoug h ibotenic acid infusion consistently produced a larger area of damage as assessed in Nissl-stained sections. Analysis of the number of ChAT -immunoreactive cells in the nucleus basalis magnocellularis (NBM) sho wed an average 60% cell loss following colchicine infusion and a 75% c ell loss after ibotenic acid infusion. Area of glutamic acid decarboxy lase (GAD) staining was significantly decreased in several regions sur rounding the NBM for ibotenic acid (51% average decrease), and showed non-significant decreases (28%) following colchicine infusion. Colchic ine infusion decreased dopamine and 3,4-dihydroxyphenylacetic acid (DO PAC) in the striatum; ibotenic acid had no effect on brain catechol or indoleamine levels. The results indicate that although similar cholin ergic hypofunction and behavioral deficits were achieved, several non- cholinergic differences between the neurotoxicants were detected.