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58

Chapter 3

between the bromocriptine and placebo session. [Reward x Switching x

DAT1

x Drug: F(1,46)

= 1.5, p > .1], [Reward x Switching x Drug: F(1,46) < 1]. The degree to which reward affected

performance irrespective of task switching [main effect Reward: response time: F(1,46) =

19.4, p < .001; error rate: F(1,46) = 20.6, p < .001] was also not modulated by bromocriptine

(error rate and response time: [Reward x Drug: F(1,46) < 1], [Reward x Drug x

DAT1

: F(1,46)

= 1.6 , p > .2]).

Neuropsychological assessments

There were no differences between the two

DAT1

genotype groups in term of age, gender, IQ,

trait impulsivity (BIS-11), depression (BDI), trait anxiety (STAI) or working memory capacity

(listening span; all p > .2) (

supplementary results: table S3.3a

), and there were no significant

correlations between any of these trait measures and drug-induced changes in performance

(all p > .2).

Listening span

Working memory capacity (measured with listening span; Daneman and Carpenter 1980,

Salthouse and Babcock 1991) has been associated with striatal dopamine synthesis capacity

(Cools et al., 2008) Moreover, previous studies have shown that dopaminergic drug effects

can be predicted from working memory capacity (Luciana et al., 1992; Kimberg et al., 1997;

Luciana and Collins, 1997; Mehta et al., 2001; Mehta et al., 2003; Mehta et al., 2004; Gibbs

and D’Esposito, 2005b, a; Cools et al., 2007a; Mehta et al., 2008). Accordingly, we assessed

drug effects as a function of listening span. To this end, we divided the group into low-span

participants (n = 23) and high-span participants (n = 25), using a median-split analysis

(

supplemental table S3.3b

). Consistent with prior work, and like the 10R

DAT1

genotype

group, the low-span group was sensitive to the beneficial effects of bromocriptine on task-

switching (Drug x Switching: F(1,22) = 4.457, p = .046). Conversely, the high-span group was

not sensitive to the effect of bromocriptine (Drug x Switching: F(1,24) < 1), similar to the

DAT1

9R group (Drug x Switching x Span: F(1, 46) = 1.2, p > .2). Moreover, in the subgroup

of low-span participants that took part in all four drug sessions, bromocriptine also reduced

the switch cost (Drug x Switching F(1,9) = 5.466, p = .044), an effect that was not present after

pre-treatment with sulpiride (Drug x Switching: F(1,9) < 1) nor after sulpiride alone (F(1,9)

= 1.06, p = .33).

Effects of drugs on mood ratings and prolactin levels

Participants reported no drug-induced changes in mood in the large sample (all p > .3) or in

the subgroup (all p > .05). There were also no significant correlations between drug-induced

changes in task performance and drug-induced changes in mood (all p > .3)

Furthermore, bromocriptine decreased plasma prolactin levels relative to placebo, whereas