The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal

Renewal describes the recovery of an extinguished response if recall is tested in a context different from the extinction context. Behavioral studies demonstrated that attention to relevant context strengthens renewal. Neurotransmitters mediating attention and learning such as the dopaminergic (DA) system presumably modulate extinction learning and renewal. However, the role of DA for non-fear-based extinction learning and renewal in humans has not yet been investigated. This fMRI study investigated effects of DA-antagonism upon context-related extinction in a predictive learning task in which extinction occurred either in a novel (ABA) or an unchanged (AAA) context. The tiapride-treated group (TIA) showed significantly impaired ABA extinction learning and a significant within-group difference between ABA and AAA extinction, compared to placebo (PLAC). Groups did not differ in their level of ABA renewal. In ABA extinction, TIA showed reduced activation in dlPFC and OFC, hippocampus, and temporal regions. Across groups, activation in PFC and hippocampus correlated negatively with ABA extinction errors. Results suggest that in context-related extinction learning DA in PFC and hippocampus is involved in readjusting the cue-outcome relationship in the presence of a novel context. However, relating context to the appropriate association during recall does not appear to rely exclusively on DA signaling.

[1]  M. Tegenthoff,et al.  The GABAergic system in prefrontal cortex and hippocampus modulates context-related extinction learning and renewal in humans , 2016, Brain Imaging and Behavior.

[2]  E. Miller,et al.  Neural Substrates of Dopamine D2 Receptor Modulated Executive Functions in the Monkey Prefrontal Cortex. , 2015, Cerebral cortex.

[3]  Oliver T. Wolf,et al.  Beta-adrenergic receptors support attention to extinction learning that occurs in the absence, but not the presence, of a context change , 2015, Front. Behav. Neurosci..

[4]  O. Güntürkün,et al.  Noradrenergic stimulation modulates activation of extinction-related brain regions and enhances contextual extinction learning without affecting renewal , 2015, Front. Behav. Neurosci..

[5]  M. Puig,et al.  Prefrontal dopamine in associative learning and memory , 2014, Neuroscience.

[6]  H. Dinse,et al.  Opposing effects of dopamine antagonism in a motor sequence task—tiapride increases cortical excitability and impairs motor learning , 2014, Front. Behav. Neurosci..

[7]  Colin D. Rey,et al.  Dopamine D1 Receptor Activation Rescues Extinction Impairments in Low-Estrogen Female Rats and Induces Cortical Layer-Specific Activation Changes in Prefrontal–Amygdala Circuits , 2014, Neuropsychopharmacology.

[8]  N. Chaudhri,et al.  Blocking dopamine d1-like receptors attenuates context-induced renewal of pavlovian-conditioned alcohol-seeking in rats. , 2014, Alcoholism, clinical and experimental research.

[9]  K. Lattal,et al.  Dopamine and extinction: A convergence of theory with fear and reward circuitry , 2014, Neurobiology of Learning and Memory.

[10]  A. Puerto,et al.  Tiapride impairs the aversive effect of electrical stimulation of the parabrachial complex in a conditioned place task. , 2014, Acta neurobiologiae experimentalis.

[11]  Martin Tegenthoff,et al.  Hippocampal activation during extinction learning predicts occurrence of the renewal effect in extinction recall , 2013, NeuroImage.

[12]  Raffael Kalisch,et al.  Single dose of l-dopa makes extinction memories context-independent and prevents the return of fear , 2013, Proceedings of the National Academy of Sciences.

[13]  Gregory G. Brown,et al.  Linking mathematical modeling with human neuroimaging to segregate verbal working memory maintenance processes from stimulus encoding. , 2013, Neuropsychology.

[14]  Harald Lachnit,et al.  The informational value of contexts affects context-dependent learning , 2013, Learning & behavior.

[15]  Koen Van Laere,et al.  Measuring extrastriatal dopamine release during a reward learning task , 2011, Human brain mapping.

[16]  J. Pearce,et al.  Contextual control of attentional allocation in human discrimination learning. , 2013, Journal of experimental psychology. Animal behavior processes.

[17]  Jonathan D. Cohen,et al.  Role of prefrontal cortex and the midbrain dopamine system in working memory updating , 2012, Proceedings of the National Academy of Sciences.

[18]  I. Izquierdo,et al.  Modulation of the extinction of two different fear-motivated tasks in three distinct brain areas , 2012, Behavioural Brain Research.

[19]  E. Miller,et al.  The Role of Prefrontal Dopamine D1 Receptors in the Neural Mechanisms of Associative Learning , 2012, Neuron.

[20]  H. Lachnit,et al.  Modulation of attention in discrimination learning: The roles of stimulus relevance and stimulus–outcome correlation , 2011, Learning & Behavior.

[21]  A. Puerto,et al.  The D2/D3-receptor antagonist tiapride impairs concurrent but not sequential taste aversion learning , 2012, Brain Research Bulletin.

[22]  J. Marshall,et al.  Dopamine D1 receptor antagonism impairs extinction of cocaine-cue memories , 2012, Behavioural Brain Research.

[23]  Lars Farde,et al.  Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans , 2011, NeuroImage.

[24]  S. Killcross,et al.  Rat prefrontal dopamine and cognitive control: impaired and enhanced conflict performance. , 2011, Behavioral neuroscience.

[25]  M. Ullsperger,et al.  Dopamine-Mediated Reinforcement Learning Signals in the Striatum and Ventromedial Prefrontal Cortex Underlie Value-Based Choices , 2011, The Journal of Neuroscience.

[26]  Andrew P. Yonelinas,et al.  Putting the Pieces Together: The Role of Dorsolateral Prefrontal Cortex in Relational Memory Encoding , 2011, Journal of Cognitive Neuroscience.

[27]  A. Cooper,et al.  Predictive Reward Signal of Dopamine Neurons , 2011 .

[28]  G. Quirk,et al.  Infralimbic D2 Receptors Are Necessary for Fear Extinction and Extinction-Related Tone Responses , 2010, Biological Psychiatry.

[29]  D. Shohamy,et al.  Dopamine and adaptive memory , 2010, Trends in Cognitive Sciences.

[30]  M. Bardo,et al.  Renewal of sucrose-seeking behavior in rats: Role of D2 dopamine receptors , 2010, Pharmacology Biochemistry and Behavior.

[31]  Jean-Luc Anton,et al.  Region of interest analysis using an SPM toolbox , 2010 .

[32]  Etienne Coutureau,et al.  A Role for Medial Prefrontal Dopaminergic Innervation in Instrumental Conditioning , 2009, The Journal of Neuroscience.

[33]  Nicole M. Lauzon,et al.  Dopamine D1 versus D4 Receptors Differentially Modulate the Encoding of Salient versus Nonsalient Emotional Information in the Medial Prefrontal Cortex , 2009, The Journal of Neuroscience.

[34]  N. Dubrovina,et al.  Effects of Activation and Blockade of Dopamine Receptors on the Extinction of a Passive Avoidance Reaction in Mice with a Depressive-Like State , 2009, Neuroscience and Behavioral Physiology.

[35]  Fumitoshi Kodaka,et al.  Differential Contributions of Prefrontal and Hippocampal Dopamine D1 and D2 Receptors in Human Cognitive Functions , 2008, The Journal of Neuroscience.

[36]  H. Lachnit,et al.  Dissociations among ABA, ABC, and AAB recovery effects. , 2008 .

[37]  I. G. Sil’kis.  The role of dopamine-dependent negative feedback in the hippocampus-basal ganglia-thalamus-hippocampus loop in the extinction of responses , 2008, Neuroscience and Behavioral Physiology.

[38]  V. Boulougouris,et al.  Serotonergic and dopaminergic modulation of attentional processes. , 2008, Progress in brain research.

[39]  JaneR . Taylor,et al.  Bidirectional modulation of goal-directed actions by prefrontal cortical dopamine. , 2007, Cerebral cortex.

[40]  S. Rauch,et al.  Recall of Fear Extinction in Humans Activates the Ventromedial Prefrontal Cortex and Hippocampus in Concert , 2007, Biological Psychiatry.

[41]  J. B. Nelson,et al.  The role of interference produced by conflicting associations in contextual control. , 2007, Journal of experimental psychology. Animal behavior processes.

[42]  Yoshiro Okubo,et al.  Memory and frontal lobe functions; possible relations with dopamine D2 receptors in the hippocampus , 2007, NeuroImage.

[43]  J. Jentsch,et al.  Dopamine D2/D3 Receptors Play a Specific Role in the Reversal of a Learned Visual Discrimination in Monkeys , 2007, Neuropsychopharmacology.

[44]  B. O'dowd,et al.  Insights into the Role of Dopamine Receptor Systems in Learning and Memory , 2007, Reviews in the neurosciences.

[45]  G. McNally,et al.  Renewal of an extinguished instrumental response: Neural correlates and the role of D1 dopamine receptors , 2006, Neuroscience.

[46]  S. Knecht,et al.  Tonic Dopaminergic Stimulation Impairs Associative Learning in Healthy Subjects , 2006, Neuropsychopharmacology.

[47]  H. Lachnit,et al.  Contextual control in discrimination reversal learning. , 2006, Journal of experimental psychology. Animal behavior processes.

[48]  Nikolaus Weiskopf,et al.  Context-Dependent Human Extinction Memory Is Mediated by a Ventromedial Prefrontal and Hippocampal Network , 2006, The Journal of Neuroscience.

[49]  J. M. Rosas,et al.  Context switch effects on acquisition and extinction in human predictive learning. , 2006, Journal of experimental psychology. Learning, memory, and cognition.

[50]  T. Norman,et al.  Single oral dose pharmacokinetics of tiapride in patients with Huntington's disease , 2006, European Journal of Clinical Pharmacology.

[51]  R. Ponnusamy,et al.  Systemic blockade of D2-like dopamine receptors facilitates extinction of conditioned fear in mice. , 2005, Learning & memory.

[52]  L. Cohen,et al.  Dopaminergic influences on formation of a motor memory , 2005, Annals of neurology.

[53]  Patrick R Hof,et al.  Mice lacking dopamine D2 and D3 receptors exhibit differential activation of prefrontal cortical neurons during tasks requiring attention. , 2005, Cerebral cortex.

[54]  Matti Laine,et al.  Frontal and Temporal Dopamine Release during Working Memory and Attention Tasks in Healthy Humans: a Positron Emission Tomography Study Using the High-Affinity Dopamine D2 Receptor Ligand [11C]FLB 457 , 2005, The Journal of Neuroscience.

[55]  P. Kelly,et al.  Autoradiographic localization of dopamine D1 and D2 receptors in the brain of several mammalian species , 2005, Journal of Neural Transmission / General Section JNT.

[56]  Pienie Zwitserlood,et al.  D-Amphetamine Boosts Language Learning Independent of its Cardiovascular and Motor Arousing Effects , 2004, Neuropsychopharmacology.

[57]  T. Robbins,et al.  Dopaminergic Modulation of Visual Attention and Working Memory in the Rodent Prefrontal Cortex , 2004, Neuropsychopharmacology.

[58]  Y. Shaham,et al.  Effect of Dopamine Receptor Antagonists on Renewal of Cocaine Seeking by Reexposure to Drug-associated Contextual Cues , 2002, Neuropsychopharmacology.

[59]  C. Price,et al.  A PET Study of Stimulus- and Task-Induced Semantic Processing , 2002, NeuroImage.

[60]  J. Wickens,et al.  A cellular mechanism of reward-related learning , 2001, Nature.

[61]  Y. Hurd,et al.  D1 and D2 dopamine receptor mRNA expression in whole hemisphere sections of the human brain , 2001, Journal of Chemical Neuroanatomy.

[62]  B. O'dowd,et al.  Prolonged fear responses in mice lacking dopamine D1 receptor , 2001, Brain Research.

[63]  Trevor W. Robbins,et al.  Enhanced and Impaired Attentional Performance After Infusion of D1 Dopaminergic Receptor Agents into Rat Prefrontal Cortex , 2000, The Journal of Neuroscience.

[64]  E. Maguire,et al.  Patterns of hippocampal‐cortical interaction dissociate temporal lobe memory subsystems , 2000, Hippocampus.

[65]  H. Lange,et al.  The benzamide tiapride: treatment of extrapyramidal motor and other clinical syndromes. , 2000, Pharmacopsychiatry.

[66]  R. Dolan,et al.  Common effects of emotional valence, arousal and attention on neural activation during visual processing of pictures , 1999, Neuropsychologia.

[67]  Joseph E LeDoux,et al.  The dopaminergic modulation of fear: quinpirole impairs the recall of emotional memories in rats. , 1999, Behavioral neuroscience.

[68]  Frederik Barkhof,et al.  Parametric fMRI analysis of visual encoding in the human medial temporal lobe , 1999, Hippocampus.

[69]  P. Sokoloff,et al.  D3 dopamine receptor mRNA is widely expressed in the human brain , 1998, Brain Research.

[70]  P. Goldman-Rakic,et al.  Down-regulation of the D1 and D5 dopamine receptors in the primate prefrontal cortex by chronic treatment with antipsychotic drugs. , 1997, The Journal of pharmacology and experimental therapeutics.

[71]  Peter Dayan,et al.  A Neural Substrate of Prediction and Reward , 1997, Science.

[72]  Stanley J Watson,et al.  Dopamine Receptor mRNA Expression in Human Striatum and Neocortex , 1996, Neuropsychopharmacology.

[73]  K. Nakamura,et al.  The primate temporal pole: its putative role in object recognition and memory , 1996, Behavioural Brain Research.

[74]  F. Benes,et al.  Cellular colocalization of dopamine D1 and D2 receptors in rat medial prefrontal cortex , 1995, Synapse.

[75]  E. Rey,et al.  Pharmacokinetics of tiapride and absolute bioavailability of three extravascular forms. , 1982, International journal of clinical pharmacology, therapy, and toxicology.

[76]  R. Bolles,et al.  Role of conditioned contextual stimuli in reinstatement of extinguished fear. , 1979, Journal of experimental psychology. Animal behavior processes.