Spatial learning deficits are not solely due to cholinergic deficits following medial septal lesions with colchicine

Abstract

Colchicine was infused bilaterally into the cerebrolateral ventricles (3.75 μg/side) or directly into the medial septum (5 μg) of adult, male Fischer-344 rats (n = 48), and effects on behavior and cholinergic markers were determined. Rats receiving intracerebroventricular acV) administration of colchicine were hyperaggressive during the first week after administration and were hyperactive when tested during 60-min sessions at weekly intervals during the first 3 weeks after colchicine treatment. ICV colchicine also interfered with the acquisition of a spatial task in the water maze. Rats receiving colchicine directly into the medial septum were also aggressive and hyperactive, but were not impaired in the acquisition of the water-maze task. It was subsequently found that direct administration and ICV administration of colchicine both decreased the number of choline acetyltransferase (ChAT) immunoreactive cells in the medial septum by at least 50% of vehicle-treated rats and decreased ChAT enzyme activity in both the right and the left hippocampus to about 50% of controllevels. However, the acetylcholinesterase (AChE) staining was more clearly decreased bilaterally in the hippocampus after ICV infusion than after direct infusion of colchicine. ICV infusion resulted in bilateral shrinkage of the lateral septum, whereas direct septal administration resulted in only unilateral damage to the lateral septum. The results ofthese experiments do not support the generally accepted hypothesis that spatial learning deficits seen in animals with medial septum lesions are solely due to a lesion-associated cholinergic deficit in the hippocampus.