Involvement of cortical projections to basolateral amygdala in context-induced reinstatement of ethanol-seeking in rats

Ethanol is the most consumed substance of abuse in the world, and its misuse may lead to the development of alcohol use disorder (AUD). High relapse rates remain a relevant problem in the treatment of AUD. Exposure to environmental cues previously associated with ethanol intake could trigger ethanol-seeking behavior. However, the neural mechanisms involved in this phenomenon are not entirely clear. In this context, cortical projections to the basolateral amygdala (BLA) play a role in appetitive and aversive learned behaviors. Therefore, we aimed to evaluate the activation of the cortical projections from the prelimbic (PL), orbitofrontal (OFC), and infralimbic (IL), to the BLA in the context-induced reinstatement of ethanol-seeking. Male Long-Evans rats were trained to self-administer 10% ethanol in Context A. Subsequently, lever pressing in the presence of the discrete cue was extinguished in Context B. After nine extinction sessions, rats underwent intracranial surgery for the unilateral injection of red fluorescent retrograde tracer into the BLA. The context-induced reinstatement of ethanol-seeking was assessed by re-exposing the rats to Context A or B under extinction conditions. Finally, we combined retrograde neuronal tracing with Fos to identify activated cortical inputs to BLA during the reinstatement of ethanol-seeking behavior. We found that PL, but not OFC or IL, retrogradely-labeled neurons from BLA presented increased Fos expression during the re-exposure to the ethanol-associated context, suggesting that PL projection to BLA is involved in the context-induced reinstatement of ethanol-seeking behavior.

[1]  M. Sekiguchi,et al.  Adolescent social isolation induces distinct changes in the medial and lateral OFC-BLA synapse and social and emotional alterations in adult mice , 2022, Neuropsychopharmacology.

[2]  T. O’Buckley,et al.  Medial prefrontal cortex-basolateral amygdala circuit dysfunction in chronic alcohol-exposed male rats , 2021, Neuropharmacology.

[3]  B. McCool.  Ethanol modulation of cortico-basolateral amygdala circuits: Neurophysiology and behavior , 2021, Neuropharmacology.

[4]  K. Wassum,et al.  The Medial Orbitofrontal Cortex–Basolateral Amygdala Circuit Regulates the Influence of Reward Cues on Adaptive Behavior and Choice , 2021, The Journal of Neuroscience.

[5]  Andrew M. Wikenheiser,et al.  A bidirectional corticoamygdala circuit for the encoding and retrieval of detailed reward memories , 2021, bioRxiv.

[6]  D. Winder,et al.  Increased Synaptic Strength and mGlu2/3 Receptor Plasticity on Mouse Prefrontal Cortex Intra-telencephalic Pyramidal Cells Following Intermittent Access to Ethanol. , 2021, Alcoholism, clinical and experimental research.

[7]  F. Cruz,et al.  Dorsal hippocampus plays a causal role in context-induced reinstatement of alcohol-seeking in rats , 2020, Behavioural Brain Research.

[8]  William W. Taylor,et al.  Effects of optogenetic photoexcitation of infralimbic cortex inputs to the basolateral amygdala on conditioned fear and extinction , 2020, Behavioural Brain Research.

[9]  David E. Moorman,et al.  Chemogenetic Inactivation of Orbitofrontal Cortex Decreases Cue-Induced Reinstatement of Ethanol and Sucrose Seeking in Male and Female Wistar Rats. , 2020, Alcoholism, clinical and experimental research.

[10]  Marieke R. Gilmartin,et al.  Prelimbic input to basolateral amygdala facilitates the acquisition of trace cued fear memory under weak training conditions , 2020, Neurobiology of Learning and Memory.

[11]  Wenhua Zhang,et al.  Identification of a prefrontal cortex-to-amygdala pathway for chronic stress-induced anxiety , 2020, Nature Communications.

[12]  D. Hermann,et al.  Investigation of brain functional connectivity to assess cognitive control over cue‐processing in Alcohol Use Disorder , 2020, Addiction biology.

[13]  B. McCool,et al.  Withdrawal from chronic ethanol exposure increases postsynaptic glutamate function of insular cortex projections to the rat basolateral amygdala , 2019, Neuropharmacology.

[14]  Y. Shaham,et al.  Separate vmPFC Ensembles Control Cocaine Self-Administration Versus Extinction in Rats , 2019, The Journal of Neuroscience.

[15]  A. Chappell,et al.  Chronic Ethanol Differentially Modulates Glutamate Release from Dorsal and Ventral Prefrontal Cortical Inputs onto Rat Basolateral Amygdala Principal Neurons , 2019, eNeuro.

[16]  Y. Shaham,et al.  Role of mu, but not delta or kappa, opioid receptors in context‐induced reinstatement of oxycodone seeking , 2018, The European journal of neuroscience.

[17]  F. Cruz,et al.  Functional inactivation of the orbitofrontal cortex disrupts context-induced reinstatement of alcohol seeking in rats. , 2018, Drug and alcohol dependence.

[18]  K. Wassum,et al.  Distinct cortical-amygdala projections drive reward value encoding and retrieval , 2018, bioRxiv.

[19]  Laura M McGarry,et al.  Prefrontal Cortex Drives Distinct Projection Neurons in the Basolateral Amygdala. , 2017, Cell reports.

[20]  F. Cruz,et al.  Inactivation of the Prelimbic Cortex Impairs the Context-Induced Reinstatement of Ethanol Seeking , 2017, Front. Pharmacol..

[21]  C. Cepeda,et al.  Basolateral Amygdala to Orbitofrontal Cortex Projections Enable Cue-Triggered Reward Expectations , 2017, The Journal of Neuroscience.

[22]  Jonathan A Sugam,et al.  Fear extinction requires infralimbic cortex projections to the basolateral amygdala , 2017, bioRxiv.

[23]  B. Sharp,et al.  Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction , 2017, Translational Psychiatry.

[24]  P. Randall,et al.  Sex differences in alcohol self-administration and relapse-like behavior in Long-Evans rats , 2017, Pharmacology Biochemistry and Behavior.

[25]  G. Stuber,et al.  Role of a Lateral Orbital Frontal Cortex-Basolateral Amygdala Circuit in Cue-Induced Cocaine-Seeking Behavior , 2017, Neuropsychopharmacology.

[26]  M. Fleury,et al.  Remission from substance use disorders: A systematic review and meta-analysis. , 2016, Drug and alcohol dependence.

[27]  Y. Shaham,et al.  Distinct Fos-Expressing Neuronal Ensembles in the Ventromedial Prefrontal Cortex Mediate Food Reward and Extinction Memories , 2016, The Journal of Neuroscience.

[28]  Y. Shaham,et al.  Role of projections from ventral subiculum to nucleus accumbens shell in context-induced reinstatement of heroin seeking in rats , 2016, Psychopharmacology.

[29]  Y. Shaham,et al.  Role of corticostriatal circuits in context-induced reinstatement of drug seeking , 2015, Brain Research.

[30]  B. Hope,et al.  Using c-fos to study neuronal ensembles in corticostriatal circuitry of addiction , 2015, Brain Research.

[31]  A. Izquierdo,et al.  The basolateral amygdala in reward learning and addiction , 2015, Neuroscience & Biobehavioral Reviews.

[32]  Y. Shaham,et al.  Context-Induced Reinstatement of Methamphetamine Seeking Is Associated with Unique Molecular Alterations in Fos-Expressing Dorsolateral Striatum Neurons , 2015, The Journal of Neuroscience.

[33]  M. Fauth-Bühler,et al.  A comparison of region-of-interest measures for extracting whole brain data using survival analysis in alcoholism as an example , 2015, Journal of Neuroscience Methods.

[34]  R. Clem,et al.  Pathway-Selective Adjustment of Prefrontal-Amygdala Transmission during Fear Encoding , 2014, The Journal of Neuroscience.

[35]  A. Bonci,et al.  A Critical Role of Lateral Hypothalamus in Context-Induced Relapse to Alcohol Seeking after Punishment-Imposed Abstinence , 2014, The Journal of Neuroscience.

[36]  Y. Shaham,et al.  Role of Nucleus Accumbens Shell Neuronal Ensembles in Context-Induced Reinstatement of Cocaine-Seeking , 2014, The Journal of Neuroscience.

[37]  R. A. Fuchs,et al.  Contribution of a Mesocorticolimbic Subcircuit to Drug Context-Induced Reinstatement of Cocaine-Seeking Behavior in Rats , 2014, Neuropsychopharmacology.

[38]  G. McNally.  Extinction of drug seeking: Neural circuits and approaches to augmentation , 2014, Neuropharmacology.

[39]  Johannes J. Letzkus,et al.  Long-Range Connectivity Defines Behavioral Specificity of Amygdala Neurons , 2014, Neuron.

[40]  Richard Apps,et al.  Structural Basis of Cerebellar Microcircuits in the Rat , 2013, The Journal of Neuroscience.

[41]  P. Janak,et al.  Unilateral inactivation of the basolateral amygdala attenuates context‐induced renewal of Pavlovian‐conditioned alcohol‐seeking , 2013, The European journal of neuroscience.

[42]  R. Constable,et al.  Disrupted ventromedial prefrontal function, alcohol craving, and subsequent relapse risk. , 2013, JAMA psychiatry.

[43]  R. Marek,et al.  The amygdala and medial prefrontal cortex: partners in the fear circuit , 2013, The Journal of physiology.

[44]  C. Winstanley,et al.  Functional Disconnection of the Orbitofrontal Cortex and Basolateral Amygdala Impairs Acquisition of a Rat Gambling Task and Disrupts Animals' Ability to Alter Decision-Making Behavior after Reinforcer Devaluation , 2013, The Journal of Neuroscience.

[45]  Joseph P. Schacht,et al.  Effects of a GABA-ergic medication combination and initial alcohol withdrawal severity on cue-elicited brain activation among treatment-seeking alcoholics , 2013, Psychopharmacology.

[46]  G. McNally,et al.  The role of medial prefrontal cortex in extinction and reinstatement of alcohol‐seeking in rats , 2013, The European journal of neuroscience.

[47]  S. Sherman,et al.  Two populations of corticothalamic and interareal corticocortical cells in the subgranular layers of the mouse primary sensory cortices , 2012, The Journal of comparative neurology.

[48]  Y. Shaham,et al.  Role of Projections from Ventral Medial Prefrontal Cortex to Nucleus Accumbens Shell in Context-Induced Reinstatement of Heroin Seeking , 2012, The Journal of Neuroscience.

[49]  A. Mohammadpoorasl,et al.  Addiction Relapse and Its Predictors: A Prospective Study , 2012 .

[50]  G. McNally,et al.  Accumbens shell AMPA receptors mediate expression of extinguished reward seeking through interactions with basolateral amygdala. , 2011, Learning & memory.

[51]  J. Widholm,et al.  Alcohol‐seeking behavior is associated with increased glutamate transmission in basolateral amygdala and nucleus accumbens as measured by glutamate‐oxidase‐coated biosensors , 2011, Addiction biology.

[52]  R. A. Fuchs,et al.  Interaction of the Basolateral Amygdala and Orbitofrontal Cortex is Critical for Drug Context-Induced Reinstatement of Cocaine-Seeking Behavior in Rats , 2011, Neuropsychopharmacology.

[53]  Y. Shaham,et al.  Ventral medial prefrontal cortex neuronal ensembles mediate context-induced relapse to heroin , 2011, Nature Neuroscience.

[54]  K. Kantak,et al.  Interaction of the rostral basolateral amygdala and prelimbic prefrontal cortex in regulating reinstatement of cocaine-seeking behavior , 2010, Pharmacology Biochemistry and Behavior.

[55]  R. See,et al.  Reversible inactivation of the basolateral amygdala, but not the dorsolateral caudate putamen, attenuates consolidation of cocaine‐cue associative learning in a reinstatement model of drug‐seeking , 2010, The European journal of neuroscience.

[56]  Francisco Sotres-Bayon,et al.  Prefrontal control of fear: more than just extinction , 2010, Current Opinion in Neurobiology.

[57]  R. Kesner,et al.  Interactions between the prefrontal cortex and amygdala during delay discounting and reversal. , 2009, Behavioral neuroscience.

[58]  R. A. Fuchs,et al.  Involvement of the lateral orbitofrontal cortex in drug context‐induced reinstatement of cocaine‐seeking behavior in rats , 2009, The European journal of neuroscience.

[59]  Y. Shaham,et al.  Context-induced relapse to drug seeking: a review , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[60]  Patricia H. Janak,et al.  Context-Induced Relapse of Conditioned Behavioral Responding to Ethanol Cues in Rats , 2008, Biological Psychiatry.

[61]  Xingbao Li,et al.  Effect of naltrexone and ondansetron on alcohol cue-induced activation of the ventral striatum in alcohol-dependent people. , 2008, Archives of general psychiatry.

[62]  A. Chappell,et al.  Chronic ethanol and withdrawal differentially modulate pre- and postsynaptic function at glutamatergic synapses in rat basolateral amygdala. , 2007, Journal of neurophysiology.

[63]  A. Lê,et al.  Effects of opioid receptor blockade on the renewal of alcohol seeking induced by context: relationship to c‐fos mRNA expression , 2007, The European journal of neuroscience.

[64]  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.

[65]  G. Schoenbaum,et al.  Basolateral Amygdala Lesions Abolish Orbitofrontal-Dependent Reversal Impairments , 2007, Neuron.

[66]  Erika B. Litvin,et al.  Relapse and relapse prevention. , 2007, Annual review of clinical psychology.

[67]  R. Moos,et al.  Rates and predictors of relapse after natural and treated remission from alcohol use disorders. , 2006, Addiction.

[68]  G. Koob,et al.  The Neurobiology of Addiction , 1997, Alcohol health and research world.

[69]  Geoffrey Schoenbaum,et al.  Rapid Associative Encoding in Basolateral Amygdala Depends on Connections with Orbitofrontal Cortex , 2005, Neuron.

[70]  H. Flor,et al.  Cue-induced activation of the striatum and medial prefrontal cortex is associated with subsequent relapse in abstinent alcoholics , 2004, Psychopharmacology.

[71]  Konstantin Voronin,et al.  Differential Brain Activity in Alcoholics and Social Drinkers to Alcohol Cues: Relationship to Craving , 2004, Neuropsychopharmacology.

[72]  J. Power,et al.  The amygdaloid complex: anatomy and physiology. , 2003, Physiological reviews.

[73]  Joselyn McLaughlin,et al.  Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats , 2003, Psychopharmacology.

[74]  R. A. Fuchs,et al.  Drug Addiction, Relapse, and the Amygdala , 2003, Annals of the New York Academy of Sciences.

[75]  T. Brandon,et al.  Effects of extinction context and retrieval cues on alcohol cue reactivity among nonalcoholic drinkers. , 2002, Journal of consulting and clinical psychology.

[76]  R. A. Fuchs,et al.  Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats , 2002, Psychopharmacology.

[77]  Jeffrey W Grimm,et al.  Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior , 2001, Psychopharmacology.

[78]  E. Murray,et al.  Control of Response Selection by Reinforcer Value Requires Interaction of Amygdala and Orbital Prefrontal Cortex , 2000, The Journal of Neuroscience.

[79]  G. Schoenbaum,et al.  Orbitofrontal Cortex and Representation of Incentive Value in Associative Learning , 1999, The Journal of Neuroscience.

[80]  R. See,et al.  Lesions of the basolateral amygdala abolish the ability of drug associated cues to reinstate responding during withdrawal from self-administered cocaine , 1997, Behavioural Brain Research.

[81]  M. Bouton,et al.  Renewal of extinguished responding in a second context , 1994 .

[82]  R. Ehrman,et al.  Classical Conditioning in Drug‐Dependent Humans a , 1992, Annals of the New York Academy of Sciences.

[83]  A. Wikler,et al.  Dynamics of drug dependence. Implications of a conditioning theory for research and treatment. , 1973, Archives of general psychiatry.

[84]  R. Sinha,et al.  The neurobiology of alcohol craving and relapse. , 2014, Handbook of clinical neurology.

[85]  C. Li,et al.  Imaging stress- and cue-induced drug and alcohol craving: association with relapse and clinical implications. , 2007, Drug and alcohol review.

[86]  P. Staiger,et al.  Cue reactivity in alcohol abusers: stimulus specificity and extinction of the responses. , 1991, Addictive behaviors.

[87]  Mark E. Bouton,et al.  Sources of relapse after extinction in Pavlovian and instrumental learning , 1991 .