title: The role of GABAB receptors in human reinforcement learning.
abstract: Behavioral evidence from human studies suggests that the γ-aminobutyric acid type B receptor (GABAB receptor) agonist baclofen modulates reinforcement learning and reduces craving in patients with addiction spectrum disorders. However, in contrast to the well established role of dopamine in reinforcement learning, the mechanisms by which the GABAB receptor influences reinforcement learning in humans remain completely unknown. To further elucidate this issue, a cross-over, double-blind, placebo-controlled study was performed in healthy human subjects (N=15) to test the effects of baclofen (20 and 50mg p.o.) on probabilistic reinforcement learning. Outcomes were the feedback-induced P2 component of the event-related potential, the feedback-related negativity, and the P300 component of the event-related potential. Baclofen produced a reduction of P2 amplitude over the course of the experiment, but did not modulate the feedback-related negativity. Furthermore, there was a trend towards increased learning after baclofen administration relative to placebo over the course of the experiment. The present results extend previous theories of reinforcement learning, which focus on the importance of mesolimbic dopamine signaling, and indicate that stimulation of cortical GABAB receptors in a fronto-parietal network leads to better attentional allocation in reinforcement learning. This observation is a first step in our understanding of how baclofen may improve reinforcement learning in healthy subjects. Further studies with bigger sample sizes are needed to corroborate this conclusion and furthermore, test this effect in patients with addiction spectrum disorder.
authors.affiliation: Neuropsychopharmacology and Brain Imaging Research Unit, University Hospital of Psychiatry Zurich, CH-8032 Zurich, Switzerland. Electronic address: Andres.Ort@uzh.ch.
authors.forename: Andres
authors.initials: A
authors.lastname: Ort
authors.affiliation: Neuropsychopharmacology and Brain Imaging Research Unit, University Hospital of Psychiatry Zurich, CH-8032 Zurich, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Kometer
authors.affiliation: Neuropsychopharmacology and Brain Imaging Research Unit, University Hospital of Psychiatry Zurich, CH-8032 Zurich, Switzerland.
authors.forename: Judith
authors.initials: J
authors.lastname: Rohde
authors.affiliation: Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, CH-8032 Zurich, Switzerland; Neuroscience Center, University and ETH Zurich, CH-8057 Zurich, Switzerland; Zurich Center for Integrative Human Physiology, CH-8057 Zurich, Switzerland.
authors.forename: Erich
authors.initials: E
authors.lastname: Seifritz
authors.affiliation: Neuropsychopharmacology and Brain Imaging Research Unit, University Hospital of Psychiatry Zurich, CH-8032 Zurich, Switzerland; Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital of Psychiatry Zurich, CH-8032 Zurich, Switzerland; Neuroscience Center, University and ETH Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Franz X
authors.initials: FX
authors.lastname: Vollenweider
mesh_terms: D000328:Adult; D001418:Baclofen / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D006801:Humans; D008297:Male; D009483:Neuropsychological Tests; D011337:Probability Learning; D011594:Psychometrics; D018080:Receptors, GABA-B / Q000378:metabolism*; D012054:Reinforcement, Psychology; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D058786:GABA-B Receptor Agonists; D018080:Receptors, GABA-B; D001418:Baclofen
keywords: Baclofen; GABA(B) receptor; P2; Reinforcement learning