The effects of dopaminergic D2-like receptor stimulation upon behavioral and neural correlates of renewal depend on individual context processing propensities

ABSTRACT Renewal is defined as the recovery of an extinguished response when the contexts of extinction and recall differ. Prominent hippocampal activity during context‐related extinction can predict renewal. Dopaminergic antagonism during extinction learning impaired extinction and reduced hippocampal activation, without affecting renewal. However, to what extent dopaminergic stimulation during extinction influences hippocampal processing and renewal is as yet unknown. In this fMRI study, we investigated the effects of the dopamine D2‐like agonist bromocriptine upon renewal in an associative learning task, in hippocampus and ventromedial PFC. We observed significant differences between bromocriptine (BROMO) and placebo (PLAC) treatments in the subgroups showing (REN) and lacking (NoREN) renewal: the renewal level of BROMO REN was significantly higher, and associated with more prominent hippocampal activation during extinction and recall, compared to PLAC REN and BROMO NoREN. Results suggest that an interaction between D2like‐agonist‐induced enhancement of hippocampal activity and a pre‐existing tendency favoring context processing contributed to the higher renewal levels. In contrast, ventromedial prefrontal activation was unchanged, indicating that increased hippocampal context processing and not prefrontal response selection constituted the central driving force behind the high renewal levels. The findings demonstrate that hippocampal dopamine is important for encoding and providing of context information, and thus crucially involved in the renewal effect. HighlightsEffects of dopaminergic stimulation upon extinction and renewal were investigatedThe dopamine agonist bromocriptine increased renewal and hippocampal activationOnly participants with a propensity for context processing showed these effectsVentromedial prefrontal activation was not affected by dopaminergic stimulationHippocampal dopamine is important for context processing and involved in renewal

[1]  A. Rivera,et al.  Dopamine D5 receptors of rat and human brain , 2000, Neuroscience.

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

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

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

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

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

[7]  Arthur P. Shimamura,et al.  Memory and frontal lobe function. , 1995 .

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

[9]  M. D’Esposito,et al.  Impulsive Personality Predicts Dopamine-Dependent Changes in Frontostriatal Activity during Component Processes of Working Memory , 2007, The Journal of Neuroscience.

[10]  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.

[11]  R. Depue,et al.  Opposing roles for dopamine and serotonin in the modulation of human spatial working memory functions. , 1998, Cerebral cortex.

[12]  T. Robbins,et al.  Serotonergic Modulation of Prefrontal Cortex during Negative Feedback in Probabilistic Reversal Learning , 2005, Neuropsychopharmacology.

[13]  O. Wolf,et al.  The DA antagonist tiapride impairs context-related extinction learning in a novel context without affecting renewal , 2015, Front. Behav. Neurosci..

[14]  J. Stout,et al.  Hippocampal 5-HT1A Receptor and Spatial Learning and Memory , 2015, Front. Pharmacol..

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

[16]  S. Belcheva,et al.  Hippocampal asymmetry in serotonergic modulation of learning and memory in rats , 2007, Laterality.

[17]  M. Bouton.  Context and behavioral processes in extinction. , 2004, Learning & memory.

[18]  J. Monti,et al.  The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking. , 2008, Progress in brain research.

[19]  M. Brandão,et al.  Medial prefrontal cortex serotonergic and GABAergic mechanisms modulate the expression of contextual fear: Intratelencephalic pathways and differential involvement of cortical subregions , 2015, Neuroscience.

[20]  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..

[21]  Martin Tegenthoff,et al.  Hippocampal Context Processing during Acquisition of a Predictive Learning Task Is Associated with Renewal in Extinction Recall , 2016, Journal of Cognitive Neuroscience.

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

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

[24]  J. Lisman,et al.  The Hippocampal-VTA Loop: Controlling the Entry of Information into Long-Term Memory , 2005, Neuron.

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

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

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

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

[29]  M. Haney,et al.  Neuroendocrine effects of d-fenfluramine and bromocriptine following repeated smoked cocaine in humans. , 2001, Drug and alcohol dependence.

[30]  A. Saykin,et al.  Dopaminergic challenge with bromocriptine one month after mild traumatic brain injury: altered working memory and BOLD response. , 2011, The Journal of neuropsychiatry and clinical neurosciences.

[31]  D. Mueller,et al.  Noradrenergic modulation of extinction learning and exposure therapy , 2010, Behavioural Brain Research.

[32]  M. Brandão,et al.  Further evidence for involvement of the dorsal hippocampus serotonergic and γ-aminobutyric acid (GABA)ergic pathways in the expression of contextual fear conditioning in rats , 2013, Journal of psychopharmacology.

[33]  Christian J. Merz,et al.  Cortisol disrupts the neural correlates of extinction recall , 2016, NeuroImage.

[34]  Simon B. Eickhoff,et al.  A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data , 2005, NeuroImage.

[35]  A. Meneses,et al.  8-OH-DPAT facilitated memory consolidation and increased hippocampal and cortical cAMP production , 2004, Behavioural Brain Research.

[36]  C. Fiebach,et al.  Dissociable fronto-striatal effects of dopamine D2 receptor stimulation on cognitive versus motor flexibility , 2013, Cortex.

[37]  Alfredo Feria-Velasco,et al.  Serotonin/dopamine interaction in memory formation. , 2008, Progress in brain research.

[38]  F. Yasuno,et al.  Inhibitory effect of hippocampal 5-HT1A receptors on human explicit memory. , 2003, The American journal of psychiatry.

[39]  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.

[40]  Mark D'Esposito,et al.  A functional MRI study of the effects of bromocriptine, a dopamine receptor agonist, on component processes of working memory , 2005, Psychopharmacology.

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

[42]  M. E. Olvera-Cortés,et al.  Serotonin/dopamine interaction in learning. , 2008, Progress in brain research.

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

[44]  M. Frank,et al.  Striatal Dopamine Predicts Outcome-Specific Reversal Learning and Its Sensitivity to Dopaminergic Drug Administration , 2009, The Journal of Neuroscience.

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

[46]  T. Robbins,et al.  The neuropsychology of ventral prefrontal cortex: Decision-making and reversal learning , 2004, Brain and Cognition.

[47]  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.

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

[49]  R. J. Darby,et al.  Effects of context on responding during a compound stimulus. , 1995, Journal of experimental psychology. Animal behavior processes.

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

[51]  H. Togashi,et al.  Facilitation of fear extinction by the 5‐HT1A receptor agonist tandospirone: Possible involvement of dopaminergic modulation , 2013, Synapse.

[52]  R. Holt,et al.  Bromocriptine: old drug, new formulation and new indication , 2010, Diabetes, obesity & metabolism.

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

[54]  F Brambilla,et al.  Neuroendocrine correlates of temperamental traits in humans , 2000, Psychoneuroendocrinology.

[55]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.