Comparison of four spatial maze learning tests with methylnitrosourea‐induced microcephaly Rats

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Abstract
The usefulness of four spatial maze learning test methods, single T‐maze, Biel water maze, Morris water maze, and radial eightarm maze, was compared using rats with different degrees of microcephaly, which were induced by single intraperitoneal injection with 3 and 5 mg/kg of methylnitrosourea (MNU) on day 13 of gestation. The single T‐maze test did not detect a learning defect in either MNU group. In the Biel water maze test, the swimming time and number of errors were increased in the 5 mg/kg group, but these parameters were comparable to the control values in the retention and path B (reverse course) tests. On the Morris water maze task, the 5 mg/kg group required longer swimming time and distance to reach the goal. In the retest with the goal set on an opposite side, the swimming distance in the 5 mg/kg group was as long as the value in the original test. The radial eight‐arm maze test detected fewer correct choices in both MNU groups, which showed different responses on this task. The brain weights in the 3 and 5 mg/kg groups were approximately 80 and 60% of the control value, respectively. The cerebral cortex weights were 77 and 50% of the control value, and the hippocampus weights were 78 and 51%. Among the four maze tests, only the radial eight‐arm maze test could detect the effect of both doses of MNU. This shows that the method has the highest sensitivity to spatial learning defect in MNU‐induced microcephalic rats.