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General discussion
6
, the demonstration that infusion of a dopamine antagonist in the striatum will impair
performance on the rewarded task-switching paradigm will further substantiate a role for
striatal dopamine in motivated cognitive control.
In
chapter 3 and 5
, we aimed to elucidate the role of specific dopamine receptors in motivated
cognitive control. Two hypotheses should be assessed in future work. First, given previous
work showing that reward-related effects of methylphenidate are blocked by a dopamine D1
antagonist, but not by dopamine D2 receptor antagonism (Meririnne et al., 2001), dopamine
D1 receptor stimulation is a likely candidate for a role in motivated cognitive control. Second,
a role for concurrent dopamine D1 and D2 receptor stimulation in reward motivation
(Ikemoto et al., 1997) has been suggested. This suggests that concurrent D1 and D2 receptor
stimulationmay also be crucial for motivated cognitive control.These hypotheses can be tested
by administration of a compound which increases dopamine levels (e.g. methylphenidate), in
combination with the pre-treatment approach we used in
chapter 3
. More specifically, in
addition to a placebo session, the administration of methylphenidate should be combined
with the pre-treatment of (1) placebo, (2) a dopamine D1 receptor antagonist, (3) a dopamine
D2 receptor antagonist and (4) a combination of both a D1 and D2 receptor antagonist.
The administration of methylphenidate after pre-treatment with a placebo is hypothesized
to improve motivated cognitive control compared with the placebo session. Pre-treatment
with a dopamine D2 receptor antagonist will not have any effect on motivated cognitive
control (
chapter 3
). However, if dopamine D1 receptor stimulation mediates the effect of
methylphenidate on motivated cognitive control, the effects of methylphenidate will be
blocked after pre-treatment with a dopamine D1 receptor antagonist. Crucially, if motivated
cognitive control is mediated by a combination of dopamine D1 and D2 receptor stimulation,
only pre-treatment of both a dopamine D1 and D2 receptor antagonist will fully block the
effects of methylphenidate. One problem however is the lack of an available dopamine
D1 agonist or antagonist for use in research with healthy human subjects. Until a suitable
pharmacological agent becomes available, the rodent paradigm presented in
chapter 6
can
be used to assess whether a dopamine D1 agonist (which
is
available for use in rodents)
affects successful motivated cognitive control. In addition, methylphenidate acts not only
on dopamine transporters, but it also blocks noradrenaline transporters. To confirm that
dopamine mediated the effects of methylphenidate, an additional session should be included
to show that the effects of methylphenidate can be blocked with co-administration of a (non-
selective) dopamine receptor antagonist.
In
chapter 1
, we proposed that motivation can have opposite effects on cognitive stability and
flexibility. Although the results in
chapter 5
are generally congruous with this idea, this should
be addressed formally in future experimental work. For example by using the reward Stroop
paradigm presented in
chapter 1
(
figure 1.3
) to contrast the effects of cognitive widening
and focusing on Stroop performance in one paradigm. Cognitive widening will be beneficial
for performance on congruent Stroop targets, whereas cognitive focussing will benefit
performance on incongruent trials. Future experimental work is necessary to reveal whether