DISRUPTION OF THE DOPAMINE-BETA-HYDROXYLASE GENE IN MICE SUGGESTS ROLES FOR NOREPINEPHRINE IN MOTOR FUNCTION, LEARNING, AND MEMORY

Mice unable to synthesize norepinephrine (NE) were created by targeted disruption of the dopamine P-hydroxylase (DBH) gene. DBH-deficient (D BH -/-) mice display normal home cage activity; however, they swim mor e slowly than their littermates, and some drown. The mutant mice also perform less well on a rapidly rotating rod, and similar to 20% do not learn to walk when the rod begins to turn. Restoration of NE with dih ydroxyphenylserine eliminated these motor deficits. DBH -/- mice exhib it normal learning and retention of a passive avoidance paradigm; howe ver, they do not master an active avoidance paradigm as readily as con trols and exhibit more rapid extinction of the active-avoidance task. DBH -/- mice learn to find the hidden platform in the Morris water maz e in spite of their slower swim speed and show normal preference for t he correct quadrant in the transfer test immediately after training. H owever, this preference declines relative to controls during the next 2 days.