Colchicine-induced granule cell loss in rat hippocampus: selective behavioral and histological alterations.

Bilateral injection of 3.5 micrograms of colchicine into two levels of the dentate gyrus produced a selective loss of dentate granule cells and persistent behavioral effects in male Fischer rats. Histological analysis confirmed that this dosage of colchicine resulted in the selective loss of most granule cells in both superior and inferior blades of the dentate gyrus near the injection sites, while sparing pyramidal cells in CA1, CA2, CA3, and CA4, and GABAergic interneurons throughout the hippocampus. Rats injected with colchicine were significantly more active than cerebrospinal fluid-injected controls 2, 7, 14, 21 and 28 days after treatment. Behavioral reactivity, assessed by the magnitude of the acoustic startle response and the latency to respond in a hot-plate test, was not affected at any of these time points. Retention of a step-through passive avoidance task was impaired in the colchicine group one month after surgery. Their step-through latencies were significantly shorter than control latencies, and they exhibited more partial entries during the retention test. Acquisition and performance in a radial-arm maze, measured up to 3 months after surgery, were also impaired by colchicine. Animals injected with colchicine required more trials to acquire the task and were less accurate in the task even after their performance had stabilized. These data suggest that the hippocampus modulates motor behavior and cognitive function. The results of these experiments also support the use of colchicine as a means of defining the functional and anatomical consequences following selective destruction of the granule cell population of the dentate gyrus.