Timecourse of the behavioral effects of L-dopa on a DD mouse
DD mouse after L-dopa from Claire Cannon on Vimeo.
A DD mouse given L-dopa (50 mg/kg) was filmed for 30 minutes. In the first 10 minutes following injection, she demonstrated signs of visceral malaise. This is typical of both DD and control mice following L-dopa injection, and has been reported in human patients given L-dopa in the absence of a peripheral decarboxylase inhibitor such as carbidopa. In mice, the species typical behavioral signs of visceral illness are elongation of the torso, contraction of the abdominal walls, dragging the belly along the cage bottom, and extension of the hindlimbs and tail. These initial effects of L-dopa are difficult to distinguish from the behavioral effects of a dose of LiCl that is able to induce taste aversion. The experience of malaise may be caused by activation of peripheral enteric, sympathetic and hindbrain DA receptors. Within 10 minutes, DD mice begin to move about the cage and are visibly hyperactive within 20 minutes of injection. The movie above depicts typical sequences from within this timecourse.
The graph below depicts the robust locomotor hyperactivity, in meters traveled, of a group of DD mice after injection with L-dopa at time zero. Prior to L-dopa injection, these mice demonstrated minimal voluntary activity. Following L-dopa, the mice demonstrate a prolonged period of vigorous hyperactivity. By comparison, the psychomotor activation induced by a large dose of cocaine in a control mouse would peak after 30 minutes, and be virtually absent after a single hour.
Long-lasting locomotor hyperactivity in DD mice following daily L-dopa. The brain DA content of DD mice after L-dopa treatment has measured once, at 2 hours and 18 hours after injection, and was reported (data not shown) in (Zhou and Palmiter, 1995). At 2 hours after L-dopa, when activity of DD mice has peaked, brain DA levels are approximately 10% of what they would be in a normal mouse. Higher doses of L-dopa induced debilitating stereotypies and self-inflicted injury, as was first observed by Ungerstedt in 6-OHDA lesioned rats. Thus, DD mice are extremely sensitive to DA. Within 18-h after L-dopa injection, Zhou and Palmiter reported that the level of DA had fallen to less than 1% that of a normal mouse. There is no hyperactivity following L-dopa in control mice. If anything, control mice are significantly less active in the hour following L-dopa injection.
The behavioral and neurophysiological effects of L-dopa are described in greater detail here.