PHARMACO-FMRI · The interplay between the appetitive dopaminergic and the aversive serotonergic system in motivational control of behavior

The interplay between the appetitive dopaminergic and the aversive serotonergic system in motivational control of behavior

1. EXECUTIVE SUMMARY Usually, good behaviour that allows us to adapt to a changing environment is rewarded, while inappropriate behaviour is punished. The neurotransmitters dopamine and serotonin modulate the impact of reward and punishment, respectively, on our behaviour. In order to better understand how these brain chemicals interact to affect the motivational control of behaviour, the PHARMACO-FMRI project was established. The research fellow involved in this project when to the Center for Functional MRI, University of California, San Diego, USA, during the outgoing phase, and to the Department of Neuropsychology and Psychopharmacology, Maastricht University, The Netherlands, during the return phase. The project is a multidisciplinary study bringing together individuals with expertise in the psychopharmacology and toxicology of behaviour. Scientists skilled in the use and development of advanced functional magnetic resonance imaging (fMRI) techniques are also involved. The effects of drug-induced changes in dopamine and serotonin on motivational learning and brain activation were studied. The drugs were used are methylphenidate (Ritalin) and escitalopram (Lexapro), which cause an increase in dopamine and serotonin availability in the brain, respectively. A scientific model was tested that predicts that an increase in dopamine will reduce reward sensitivity and increase punishment sensitivity, and that on the other hand an increase in serotonin will increase reward sensitivity and reduced punishment sensitivity. Brain activity under drug conditions was compared to brain activity under placebo conditions. In addition, new fMRI techniques, including arterial spin labelling (ASL) were used. The behavioral results showed no drug-induced changes in reward and punishment sensitivity. Interestingly, Ritalin improved learning of more difficult stimulus-response associations. When investigating the associated brain activity, it was found that Ritalin reduced reward-related brain activity in a brain region important for reward-processing, the striatum. No other effects of drug on brain activation were found. The results of a study into the effects of Ritalin on reward and punishment-related brain activation during a gambling task, did not find drug effects for reward and punishment-related striatal activation. However, a reduction in striatal brain activation with feedback in general (across feedback types) was found, but only when the Ritalin session was the first test session. So, in contrast with the predictions of the proposed model, increases in baseline levels of dopamine and serotonin do not seem to influence reward and punishment sensitivity for feedback in general. However, if the task on hand is new or learning of more difficult stimulus-response association is involved, increases in dopaminergic levels might improve task performance and modulate the underlying brain activity. Manuscripts are now being prepared for publication.

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