Retrieval-induced NMDA receptor-dependent Arc expression in two models of cocaine-cue memory

The association of environmental cues with drugs of abuse results in persistent drug-cue memories. These memories contribute significantly to relapse among addicts. While conditioned place preference (CPP) is a well-established paradigm frequently used to examine the modulation of drug-cue memories, very few studies have used the non-preference-based model conditioned activity (CA) for this purpose. Here, we used both experimental approaches to investigate the neural substrates of cocaine-cue memories. First, we directly compared, in a consistent setting, the involvement of cortical and subcortical brain regions in cocaine-cue memory retrieval by quantifying activity-regulated cytoskeletal-associated (Arc) protein expression in both the CPP and CA models. Second, because NMDA receptor activation is required for Arc expression, we investigated the NMDA receptor dependency of memory persistence using the CA model. In both the CPP and CA models, drug-paired animals showed significant increases in Arc immunoreactivity in regions of the frontal cortex and amygdala compared to unpaired controls. Additionally, administration of a NMDA receptor antagonist (MK-801 or memantine) immediately after cocaine-CA memory reactivation impaired the subsequent conditioned locomotion associated with the cocaine-paired environment. The enhanced Arc expression evident in a subset of corticolimbic regions after retrieval of a cocaine-context memory, observed in both the CPP and CA paradigms, likely signifies that these regions: (i) are activated during retrieval of these memories irrespective of preference-based decisions, and (ii) undergo neuroplasticity in order to update information about cues previously associated with cocaine. This study also establishes the involvement of NMDA receptors in maintaining memories established using the CA model, a characteristic previously demonstrated using CPP. Overall, these results demonstrate the utility of the CA model for studies of cocaine-context memory and suggest the involvement of an NMDA receptor-dependent Arc induction pathway in drug-cue memory interference.

[1]  H S Chen,et al.  Mechanism of memantine block of NMDA‐activated channels in rat retinal ganglion cells: uncompetitive antagonism. , 1997, The Journal of physiology.

[2]  S. Warach,et al.  Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[3]  Y. Dudai,et al.  Stability of Retrieved Memory: Inverse Correlation with Trace Dominance , 2003, Science.

[4]  R. See,et al.  Neural substrates of conditioned-cued relapse to drug-seeking behavior , 2002, Pharmacology Biochemistry and Behavior.

[5]  J. Stewart,et al.  Development of both conditioning and sensitization of the behavioral activating effects of amphetamine is blocked by the non-competitive NMDA receptor antagonist, MK-801 , 2005, Psychopharmacology.

[6]  David K Bilkey,et al.  Neurons in the Rat Anterior Cingulate Cortex Dynamically Encode Cost–Benefit in a Spatial Decision-Making Task , 2010, The Journal of Neuroscience.

[7]  J. McGinty,et al.  Relapse to cocaine-seeking increases activity-regulated gene expression differentially in the striatum and cerebral cortex of rats following short or long periods of abstinence , 2008, Brain Structure and Function.

[8]  J. D. McGaugh,et al.  Inhibition of Activity-Dependent Arc Protein Expression in the Rat Hippocampus Impairs the Maintenance of Long-Term Potentiation and the Consolidation of Long-Term Memory , 2000, The Journal of Neuroscience.

[9]  J. D. McGaugh,et al.  Anisomycin infused into the hippocampus fails to block "reconsolidation" but impairs extinction: the role of re-exposure duration. , 2006, Learning & memory.

[10]  Oswald Steward,et al.  Synaptic Activation Causes the mRNA for the IEG Arc to Localize Selectively near Activated Postsynaptic Sites on Dendrites , 1998, Neuron.

[11]  J. D. McGaugh,et al.  Memory-enhancing effects of post-training dipivefrin and epinephrine: Involvement of peripheral and central adrenergic receptors , 1992, Brain Research.

[12]  R. A. Fuchs,et al.  The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats , 2005, Neuropsychopharmacology.

[13]  J. D. McGaugh,et al.  Memory-influencing intra-basolateral amygdala drug infusions modulate expression of Arc protein in the hippocampus. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[14]  James L. McGaugh,et al.  The amygdala modulates memory for changes in reward magnitude: involvement of the amygdaloid GABAergic system , 1996, Behavioural Brain Research.

[15]  Cristina M. Alberini,et al.  Memory Retrieval and the Passage of Time: From Reconsolidation and Strengthening to Extinction , 2011, The Journal of Neuroscience.

[16]  R. Ehrman,et al.  Conditioned craving and arousal in cocaine addiction: a preliminary report. , 1988, NIDA research monograph.

[17]  Timothy E. J. Behrens,et al.  Optimal decision making and the anterior cingulate cortex , 2006, Nature Neuroscience.

[18]  Carol A Barnes,et al.  Spatial Exploration-Induced Arc mRNA and Protein Expression: Evidence for Selective, Network-Specific Reactivation , 2005, The Journal of Neuroscience.

[19]  J. Marshall,et al.  Common influences of non-competitive NMDA receptor antagonists on the consolidation and reconsolidation of cocaine-cue memory , 2012, Psychopharmacology.

[20]  L. Herbette,et al.  Interaction of the NMDA receptor noncompetitive antagonist MK-801 with model and native membranes. , 1994, Biophysical journal.

[21]  C. Parsons,et al.  Memantine is a clinically well tolerated N-methyl-d-aspartate (NMDA) receptor antagonist—a review of preclinical data , 1999, Neuropharmacology.

[22]  S. Nakanishi,et al.  Alteration of Ca2+ permeability and sensitivity to Mg2+ and channel blockers by a single amino acid substitution in the N-methyl-D-aspartate receptor. , 1993, The Journal of biological chemistry.

[23]  S. Ishii,et al.  Resolution of Uncertainty in Prefrontal Cortex , 2006, Neuron.

[24]  B. Everitt,et al.  Disrupting Reconsolidation of Drug Memories Reduces Cocaine-Seeking Behavior , 2005, Neuron.

[25]  J. Mcgaugh.  Neuromodulatory systems and the regulation of memory storage. , 1992 .

[26]  Effects of selective drugs for dopaminergic D1 and D2 receptors on conditioned locomotion in rats , 2006, Psychopharmacology.

[27]  A. Kelley,et al.  Contextual cues associated with nicotine administration increase arc mRNA expression in corticolimbic areas of the rat brain , 2005, The European journal of neuroscience.

[28]  W. Schmidt,et al.  Memantine does not substantially affect brain stimulation reward: comparison with MK-801 , 1999, Brain Research.

[29]  M. Rodríguez-Arias,et al.  Effects of NMDA receptor antagonists (MK-801 and memantine) on the acquisition of morphine-induced conditioned place preference in mice , 2004, Progress in Neuro-Psychopharmacology and Biological Psychiatry.

[30]  J. Peters,et al.  Infralimbic Prefrontal Cortex Is Responsible for Inhibiting Cocaine Seeking in Extinguished Rats , 2008, The Journal of Neuroscience.

[31]  E. Audinat,et al.  Afferent connections of the medial frontal cortex of the rat. II. Cortical and subcortical afferents , 1995, The Journal of comparative neurology.

[32]  J. Marshall,et al.  Role of Dopamine D1 Receptors in the Activation of Nucleus Accumbens Extracellular Signal-Regulated Kinase (ERK) by Cocaine-Paired Contextual Cues , 2011, Neuropsychopharmacology.

[33]  Timothy Edward John Behrens,et al.  Effort-Based Cost–Benefit Valuation and the Human Brain , 2009, The Journal of Neuroscience.

[34]  A. McDonald.  Cortical pathways to the mammalian amygdala , 1998, Progress in Neurobiology.

[35]  J. McGinty,et al.  Context-driven cocaine-seeking in abstinent rats increases activity-regulated gene expression in the basolateral amygdala and dorsal hippocampus differentially following short and long periods of abstinence , 2010, Neuroscience.

[36]  E. Zvartau,et al.  Effects of N ‐methyl‐d‐aspartate receptor antagonists on reinstatement of cocaine‐seeking behavior by priming injections of cocaine or exposures to cocaine‐associated cues in rats , 2000, Behavioural pharmacology.

[37]  Satoshi Kida,et al.  Brain Region-Specific Gene Expression Activation Required for Reconsolidation and Extinction of Contextual Fear Memory , 2009, The Journal of Neuroscience.

[38]  Carol A Barnes,et al.  Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites , 1995, Neuron.

[39]  P. Worley,et al.  Differential Intracellular Sorting of Immediate Early Gene mRNAs Depends on Signals in the mRNA Sequence , 1998, The Journal of Neuroscience.

[40]  J. Joyce,et al.  Upregulation of Arc mRNA expression in the prefrontal cortex following cue‐induced reinstatement of extinguished cocaine‐seeking behavior , 2008, Synapse.

[41]  B. Everitt,et al.  Intra-Amygdala and Systemic Antagonism of NMDA Receptors Prevents the Reconsolidation of Drug-Associated Memory and Impairs Subsequently Both Novel and Previously Acquired Drug-Seeking Behaviors , 2008, The Journal of Neuroscience.

[42]  G. Galloway,et al.  Craving predicts use during treatment for methamphetamine dependence: a prospective, repeated-measures, within-subject analysis. , 2001, Drug and alcohol dependence.

[43]  B. Everitt,et al.  Double dissociations of the effects of amygdala and insular cortex lesions on conditioned taste aversion, passive avoidance, and neophobia in the rat using the excitotoxin ibotenic acid. , 1988, Behavioral neuroscience.

[44]  G. Quirk,et al.  Consolidation of Fear Extinction Requires NMDA Receptor-Dependent Bursting in the Ventromedial Prefrontal Cortex , 2007, Neuron.

[45]  R. Beninger,et al.  Pimozide blocks establishment but not expression of amphetamine-produced environment-specific conditioning. , 1983, Science.

[46]  C. M. Holloway,et al.  Post-training disruption of Arc protein expression in the anterior cingulate cortex impairs long-term memory for inhibitory avoidance training , 2011, Neurobiology of Learning and Memory.

[47]  A. Dickinson,et al.  Cocaine seeking by rats is a goal-directed action. , 2001, Behavioral neuroscience.

[48]  O. Steward,et al.  Selective Targeting of Newly Synthesized Arc mRNA to Active Synapses Requires NMDA Receptor Activation , 2001, Neuron.

[49]  G. Paxinos,et al.  The Rat Brain in Stereotaxic Coordinates , 1983 .

[50]  M. E. Pedreira,et al.  Protein Synthesis Subserves Reconsolidation or Extinction Depending on Reminder Duration , 2003, Neuron.

[51]  R. Beninger,et al.  Pimozide blocks establishment but not expression of cocaine-produced environment-specific conditioning. , 1986, Life sciences.

[52]  J. Marshall,et al.  Altered Prelimbic Cortex Output during Cue-Elicited Drug Seeking , 2004, The Journal of Neuroscience.

[53]  Alcino J. Silva,et al.  Memory Reconsolidation and Extinction Have Distinct Temporal and Biochemical Signatures , 2004, The Journal of Neuroscience.

[54]  B. Everitt,et al.  Cue-Induced Cocaine Seeking and Relapse Are Reduced by Disruption of Drug Memory Reconsolidation , 2006, The Journal of Neuroscience.

[55]  R. A. Fuchs,et al.  Interactions of the basolateral amygdala with the dorsal hippocampus and dorsomedial prefrontal cortex regulate drug context‐induced reinstatement of cocaine‐seeking in rats , 2007, The European journal of neuroscience.

[56]  L. Cervo,et al.  Effects of dopaminergic and glutamatergic receptor antagonists on the establishment and expression of conditioned locomotion to cocaine in rats , 1996, Brain Research.

[57]  P. E. Gold,et al.  Enhancement and impairment of memory processes with post-trial injections of adrenocorticotrophic hormone. , 1976, Behavioral biology.

[58]  E. Zvartau,et al.  Intraaccumbens administration of NMDA receptor antagonist (±)-CPP prevents locomotor activation conditioned by morphine and amphetamine in rats , 1996, Pharmacology Biochemistry and Behavior.

[59]  R. A. Fuchs,et al.  Dorsal hippocampal regulation of memory reconsolidation processes that facilitate drug context‐induced cocaine‐seeking behavior in rats , 2009, The European journal of neuroscience.

[60]  J. Marshall,et al.  Molecular Substrates for Retrieval and Reconsolidation of Cocaine-Associated Contextual Memory , 2005, Neuron.

[61]  J. Peters,et al.  Extinction circuits for fear and addiction overlap in prefrontal cortex. , 2009, Learning & memory.

[62]  H. Manji,et al.  Arc Regulates Experience-Dependent Persistent Firing Patterns in Frontal Cortex , 2014, The Journal of Neuroscience.

[63]  M. Walton,et al.  Interactions between decision making and performance monitoring within prefrontal cortex , 2004, Nature Neuroscience.

[64]  E. Procyk,et al.  Reward encoding in the monkey anterior cingulate cortex. , 2006, Cerebral cortex.