Behavioural and physiological measures of the effects of dopamine on novelty processing

Several pieces of evidence have suggested that mesocortical dopamine (DA) plays
a role in the processing of novel stimuli (Duzel, Bunzeck, Guitart-Masip, &
Duzel, 2010). For example, gene polymorphisms related with high levels of DA
correlate with enhanced frontally expressed P3 ERP component, a
psychophysiological marker of novelty processing (Garcia-Garcia, Clemente,
Dominguez-Borras, & Escera, 2010). However, these studies are mainly
correlational, and no study has yet been done in which dopamine levels were
manipulated to assess the effect on novelty processing.
Apomorphine is an agonist of both the D1 and D2 receptor families, which are
abundant in areas important for cognition. If an increase in DA release affects
novelty processing, it is thus likely that administration of Apomorphine will
have similar effects.

The present project aims to determine the role of DA transmission in
novelty-related responses, both behavioral and psychophysiological. Such
findings can yield new insights into pathologies in which a disruption of
novelty processing is a central feature (e.g. schizophrenia).

Counter balanced within-subject (placebo controlled) design, in which healthy
participants will undergo a battery of cognitive tests, once after
administration of Apomorphine, and once after administration of a placebo. The
battery consists of a verbal learning task, in which words are presented
visually while standard and novel sounds are presented in the background, and a
visual paired comparison task in which participants can choose to look at
either novel polygons or at already seen polygons.

Participants will visit the EEG laboratory of the Faculty of Psychology (Van
der Boechorststraat 1 building), on two separate occasions with 7 days in
between to avoid carryover and reduce practice effects.

Pre-Testing: A personality questionnaire will be filled out before the first
session by the internet, as a requirement for registration in the study. Before
the intake of the drug, people will be tested with a memory span task, to
determine their baseline level.

Day 1: First EEG recording. Half of the participants will receive Apomorphine
(0.005 mg/kg) + domperidone (40 mg per 80 kg), and the other half placebo, in a
double blinded way. Participants will be asked to perform two tasks: an
audiovisual task to evaluate the Von Restorff effect, and a visual paired
comparison task.

Day 2: Second EEG recording. Same as day one, but the groups receiving placebo
and drug will be inverted.

None of the measurements causes any significant risk to health or long-term
well-being of the participants. It has been reported that, even at low doses,
Apomorphine can induce nausea, vomiting and weariness (Schellekens, et al.,
2010; Schellekens, et al., 2009). For this reason, the pretreatment with
domperidone will be administered (Costa, et al., 2003; Muller, et al., 2002).
Domperidone, a peripheral D2 antagonist, has no reported long-term effects,
either in experimental conditions or in long lasting treatments for Parkinson*s
disease (Braun, Cawello, Boekens, & Horstmann, 2009).