Ms. Cousins et Jd. Salamone, INVOLVEMENT OF VENTROLATERAL STRIATAL DOPAMINE IN MOVEMENT INITIATIONAND EXECUTION - A MICRODIALYSIS AND BEHAVIORAL INVESTIGATION, Neuroscience, 70(4), 1996, pp. 849-859
Previous studies have demonstrated that the ventrolateral region of th
e rat neostriatum is the site at which dopamine depletions produce pro
found motor deficits that interfere with food handling and lever press
ing. In the present work, two experiments were undertaken to investiga
te the role of ventrolateral striatal dopamine in lever pressing. The
first experiment was a detailed characterization of the motor impairme
nts induced by injections of the neurotoxic agent 6-hydroxydopamine in
to the ventrolateral striatum. Behavioral output during lever pressing
on a fixed ratio 5 schedule was recorded by a computerized system tha
t measured the duration and response initiation time for each lever pr
ess. Response initiation time was defined as the time from offset of o
ne lever press to the onset of the next one. Dopamine depletions resul
ting from 6-hydroxydopamine injections profoundly depressed lever pres
sing response tate. This deficit was largely due to a dramatic increas
e in the average response initiation time. Analysis of the distributio
n of response initiation times indicated that dopamine-depleted rats m
ade relatively few responses with fast initiation times (e.g. 0-125 ms
), and also that dopamine depletions led to a dramatic increase in the
number of pauses in responding (i.e. response initiation times greate
r than 2.5 s). This slowing of the initiation of movement was very sen
sitive to the effects of dopamine depletions, and even animals with mi
ld dopamine depletions (29.1% of control levels) showed increased init
iation times. Analysis of response durations indicated that dopamine d
epletions resulted in a shift in the distribution of durations such th
at depleted rats had a modal response duration of 375-500 ms, in contr
ast to the control mode of 125-250 ms. There was an overall increase i
n average response duration among animals with more severe dopamine de
pletions, although rats with moderate depletions showed no change in a
verage response duration. In the second experiment, in vivo dialysis m
ethods were used to study the dynamic activity of ventrolateral striat
al dopamine during lever pressing. During the performance of a 30-min
fixed ratio 5 lever pressing session, there was a small but significan
t increase (20.9% above baseline) in dopamine release. There was not a
linear or curvilinear correlation between lever pressing rate and inc
reases in dopamine release. The relatively modest increase in ventrola
teral striatal dopamine release during lever pressing and the lack of
relation between dopamine release and behavioral output may indicate t
hat dopamine in the ventrolateral striatum plays mainly a permissive r
ole in lever pressing. These results suggest that ventrolateral striat
al dopamine depletions in rats produce deficits in skilled motor contr
ol that are similar to the motor deficits observed in patients with Pa
rkinson's disease.