Skilled motor deficits in rats induced by ventrolateral striatal dopamine depletions: behavioral and pharmacological characterization

Abstract

Rats were tested in an instrumental lever pressing procedure, in which a computer program recorded detailed parameters of responding such as response initiation and duration. Initially, rats with ventrolateral striatal dopamine depletions and control rats were tested on days 3–5 after surgery. Dopamine depletions produced by local injections of 6-hydroxydopamine substantially reduced the number of lever presses emitted. Dopamine depleted animals showed significant increases in average response initiation times, average length of fast initiation times, average length of pauses and total pause time. The distribution of initiation times was altered so that DA depleted rats showed significant reductions in the relative number of very high rate responses and also showed increases in the relative number of pauses. On day 7 after surgery, dopamine-depleted rats received one of three drug treatments: injections of ascorbate vehicle, injections of 20.0 mg/kg l-DOPA, and injections of 40.0 mg/kg l-DOPA. Injections of 40.0 mg/kg l-DOPA led to some improvement in several parameters of instrumental responding. Compared to the previous baseline day, the group that received 40.0 mg/kg l-DOPA showed a significant increase in number of responses on the drug treatment day, and also showed significant decreases in average response initiation time and total pause time. The group that received 40.0 mg/kg l-DOPA also showed significant increases in number of responses (expressed as a percent of the previous day) when compared to the control group that received injections of ascorbate vehicle. These results indicate that l-DOPA can partially reverse the skilled motor deficits produced by ventrolateral striatal dopamine depletions, and suggest that this test may be useful for the assessment of antiparkinsonian drugs.