Direct Interactions between the Basolateral Amygdala and Nucleus Accumbens Core Underlie Cocaine-Seeking Behavior by Rats

An insidious feature of drug craving and drug seeking in humans is that it can be induced and maintained by conditioned stimuli after a prolonged drug-free period. Understanding the neural basis of this control over addictive behavior may aid in the development of treatments targeting drug seeking and thereby be beneficial in preventing drug use. In the present study, we used a well established animal model to investigate the functional importance of amygdala-nucleus accumbens interactions in cocaine seeking under the control of drug-associated conditioned reinforcers. To probe the direct neuroanatomical relationship between these structures within a functional corticostriatal loop, we used a neuropharmacological disconnection procedure. Thus, infusing a dopamine receptor antagonist unilaterally into the basolateral amygdala (which had no effect on its own) and an AMPA-kainate (KA) receptor antagonist into the contralateral nucleus accumbens core (which also had no effect on its own) greatly reduced cocaine seeking. We also show that bilateral infusions of the DA receptor antagonist into the amygdala, but not nucleus accumbens, or of the AMPA-KA receptor antagonist in the nucleus accumbens, but not the amygdala, also greatly reduced cocaine seeking. The results of this study demonstrate an amygdala-nucleus accumbens system that critically underlies stimulus-controlled cocaine seeking and indicate possible neurochemical targets for relapse-prevention medication.

• Publication year

  2004

• Venue

  Journal of Neuroscience

• Publication date

  2004-08-11

• Fields of study

  Biology, Medicine, Psychology

• Identifiers
  DOI 10.1523/JNEUROSCI.1581-04.2004PMID 15306650PMCID PMC6729170
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Excitotoxic lesions of the basolateral amygdala impair the acquisition of cocaine-seeking behaviour under a second-order schedule of reinforcement

  2008cited by this paper
• Restoration of spatial working memory by genetic rescue of GluR-A–deficient mice

  2005cited by this paper
• Relative roles of ventral striatal D1 and D2 dopamine receptors in responding with conditioned reinforcement

  2005cited by this paper
• Differential control over cocaine-seeking behavior by nucleus accumbens core and shell

  2004cited by this paper
• Differential involvement of the core and shell subregions of the nucleus accumbens in conditioned cue-induced reinstatement of cocaine seeking in rats

  2004cited by this paper
• Control of eye orientation: where does the brain's role end and the muscle's begin?

  2004cited by this paper
• Reinstatement of cocaine-reinforced responding in the rat

  2004cited by this paper
• Prefrontal Cortical–Ventral Striatal Interactions Involved in Affective Modulation of Attentional Performance: Implications for Corticostriatal Circuit Function

  2004cited by this paper
• Lesions of dorsolateral striatum preserve outcome expectancy but disrupt habit formation in instrumental learning

  2004cited by this paper
• Contribution of the ventral tegmental area to cocaine‐seeking maintained by a drug‐paired conditioned stimulus in rats

  2004influential reference
• 6-Hydroxydopamine lesions of the nucleus accumbens, but not of the caudate nucleus, attenuate enhanced responding with reward-related stimuli produced by intra-accumbens d-amphetamine

  2004cited by this paper
• Differential Involvement of Orbitofrontal Cortex Subregions in Conditioned Cue-Induced and Cocaine-Primed Reinstatement of Cocaine Seeking in Rats

  2004cited by this paper
• The reinstatement model of drug relapse: history, methodology and major findings

  2003cited by this paper
• Differential control over drug-seeking behavior by drug-associated conditioned reinforcers and discriminative stimuli predictive of drug availability.

  2003cited by this paper
• Selective inactivation of the dorsomedial prefrontal cortex and the basolateral amygdala attenuates conditioned-cued reinstatement of extinguished cocaine-seeking behavior in rats

  2003cited by this paper
• Lesions of the Orbitofrontal but not Medial Prefrontal Cortex Disrupt Conditioned Reinforcement in Primates

  2003cited by this paper
• Prefrontal Glutamate Release into the Core of the Nucleus Accumbens Mediates Cocaine-Induced Reinstatement of Drug-Seeking Behavior

  2003cited by this paper
• Immunohistochemical assessment of mesotelencephalic dopamine activity during the acquisition and expression of Pavlovian versus instrumental behaviours.

  2003influential reference
• Drug Addiction, Relapse, and the Amygdala

  2003cited by this paper
• Brain circuitry and the reinstatement of cocaine-seeking behavior

  2003influential reference
• Disconnection of the basolateral amygdala complex and nucleus accumbens impairs appetitive pavlovian second-order conditioned responses.

  2002cited by this paper
• Dopamine Release in the Dorsal Striatum during Cocaine-Seeking Behavior under the Control of a Drug-Associated Cue

  2002cited by this paper
• Neural substrates of conditioned-cued relapse to drug-seeking behavior.

  2002cited by this paper
• Emotion and motivation: the role of the amygdala, ventral striatum, and prefrontal cortex.

  2002cited by this paper
• Second-order schedules of drug self-administration in animals

  2002cited by this paper
• Differential Involvement of NMDA, AMPA/Kainate, and Dopamine Receptors in the Nucleus Accumbens Core in the Acquisition and Performance of Pavlovian Approach Behavior

  2001influential reference
• Changes in dopamine efflux associated with extinction, CS-induced and d-amphetamine-induced reinstatement of drug-seeking behavior by rats.

  2001influential reference
• The Circuitry Mediating Cocaine-Induced Reinstatement of Drug-Seeking Behavior

  2001cited by this paper
• Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior

  2001influential reference
• Dissociable Effects of Antagonism of NMDA and AMPA/KA Receptors in the Nucleus Accumbens Core and Shell on Cocaine-seeking Behavior

  2001influential reference
• Control of cocaine-seeking behavior by drug-associated stimuli in rats: effects on recovery of extinguished operant-responding and extracellular dopamine levels in amygdala and nucleus accumbens.

  2000influential reference
• Dissociation in Conditioned Dopamine Release in the Nucleus Accumbens Core and Shell in Response to Cocaine Cues and during Cocaine-Seeking Behavior in Rats

  2000influential reference
• Second-order schedules of drug reinforcement in rats and monkeys: measurement of reinforcing efficacy and drug-seeking behaviour

  2000cited by this paper
• Disconnection of the anterior cingulate cortex and nucleus accumbens core impairs Pavlovian approach behavior: further evidence for limbic cortical-ventral striatopallidal systems.

  2000influential reference
• Dissociation in Effects of Lesions of the Nucleus Accumbens Core and Shell on Appetitive Pavlovian Approach Behavior and the Potentiation of Conditioned Reinforcement and Locomotor Activity byd-Amphetamine

  1999influential reference
• Double dissociation of the behavioural effects of R(+) 7–OH–DPAT infusions in the central and basolateral amygdala nuclei upon Pavlovian and instrumental conditioned appetitive behaviours

  1998cited by this paper
• Conditioned changes in dopamine oxidation currents in the nucleus accumbens of rats by stimuli paired with self‐administration or yoked‐administration of d‐amphetamine

  1998influential reference
• Acquisition, maintenance and reinstatement of intravenous cocaine self-administration under a second-order schedule of reinforcement in rats: effects of conditioned cues and continuous access to cocaine

  1998influential reference
• Effects of medial prefrontal or anterior cingulate cortex lesions on responding for cocaine under fixed-ratio and second-order schedules of reinforcement in rats

  1997cited by this paper
• The Role of an Amygdalo-Nigrostriatal Pathway in Associative Learning

  1997cited by this paper
• Enhanced stimulus-reward learning by intra-amygdala administration of a D3 dopamine receptor agonist

  1997cited by this paper
• Design and analysis

  1997cited by this paper
• Excitotoxic lesions of the basolateral amygdala impair the acquisition of cocaine-seeking behaviour under a second-order schedule of reinforcement

  1996cited by this paper
• Addictive drugs as reinforcers: multiple partial actions on memory systems.

  1996cited by this paper
• Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine.

  1996cited by this paper
• The nucleus accumbens: gateway for limbic structures to reach the motor system?

  1996cited by this paper
• Dopamine Overflow in the Nucleus Accumbens during Extinction and Reinstatement of Cocaine Self-Administration Behavior

  1996influential reference
• Microinjections of flupenthixol into the caudate-putamen but not the nucleus accumbens, amygdala or frontal cortex of rats produce intra-session declines in food-rewarded operant responding.

  1993cited by this paper
• The basolateral amygdala-ventral striatal system and conditioned place preference: further evidence of limbic-striatal interactions underlying reward-related processes.

  1991cited by this paper
• The Rat Brain in Stereotaxic Coordinates

  1983cited by this paper
• The Rat Brain in Stereotaxic Coordinates

  1983cited by this paper
• AChE-stained horizontal sections of the rat brain in stereotaxic coordinates.

  1980cited by this paper
• Fixed-interval responding under second-order schedules of food presentation or cocaine injection.

  1977cited by this paper
• Second-order schedules of drug injection.

  1975cited by this paper
• Design and Analysis: A Researcher's Handbook

  1973influential reference
• Operant behavior : areas of research and application

  1966cited by this paper

• Inhibition of Slc17a7 expressing neurons in the basolateral amygdala which project to the nucleus accumbens shapes the fidelity of motivated behavior

  2026cites this paper
• High Gamma Activity in the Infralimbic Cortex to Nucleus Accumbens Shell Pathway Modulates Innate Aversion Differentially across Sex

  2025cites this paper
• Drug‐Related Engrams and Their Role in the Persistence and Recurrence of Drug‐Related Behaviors

  2025cites this paper
• FGF21 analogue PF-05231023 on alcohol consumption and neuronal activity in the nucleus accumbens

  2025cites this paper
• Do AMPA/kainate antagonists possess potential in the treatment of addiction? Evidence from animal behavioural studies.

  2025influential citation
• Pairing extinction training with vagus nerve stimulation (VNS) reduces drug-seeking by altering activity in afferents to the medial prefrontal cortex

  2025cites this paper
• Amygdala–Ventral Striatum Functional Connectivity Underlies Craving in Gambling Disorder: A Mediating Role of Depressive Symptoms

  2025cites this paper
• Neuropeptide Y neurons in the basolateral amygdala project to the nucleus accumbens and stimulate high-fat intake

  2025cites this paper
• A nociceptive amygdala-striatal pathway modulating affective-motivational pain

  2025cites this paper
• Cell-type specific epigenetic and transcriptional mechanisms in substance use disorder

  2025cites this paper
• Plasticity of ventral tegmental area disturbance during abstinence after repeated amphetamine exposure: restoration by selective activation of group II metabotropic glutamate receptors

  2025cites this paper
• Persistent enhancement of basolateral amygdala-dorsomedial striatum synapses causes compulsive-like behaviors in mice

  2024cites this paper
• Sex Differences in Oscillatory Signaling Dynamics in the Prelimbic Cortex, and Nucleus Accumbens Core during Negative Affect.

  2024cites this paper
• A nociceptive amygdala-striatal pathway for chronic pain aversion

  2024cites this paper
• Understanding the shift to compulsion in addiction: insights from personality traits, social factors, and neurobiology

  2024cites this paper
• The effect of CNQX on self-administration: present in nicotine, absent in methamphetamine model

  2024cites this paper
• Neurometabolic profile of the amygdala in smokers assessed with 1H-magnetic resonance spectroscopy

  2024cites this paper
• Emotional vocalizations alter behaviors and neurochemical release into the amygdala

  2024cites this paper
• Coordinating brain-distributed network activities in memory resistant to extinction

  2023cites this paper
• A novel perspective on the role of nucleus accumbens neurons in encoding associative learning

  2023cites this paper
• Inhibitory and excitatory alcohol-seeking cues distinct roles in behavior, neurochemistry, and mesolimbic pathway in alcohol preferring (P) rats.

  2023cites this paper
• Cue- versus reward-encoding basolateral amygdala projections to nucleus accumbens

  2023cites this paper
• The excitatory transmission from basolateral nuclues of amygdala to nucleus accumbens shell regulates propofol self‐administration through AMPA receptors

  2023cites this paper
• Accentuated Paralimbic and Reduced Mesolimbic D2/3-Impulsivity Associations in Parkinson's Disease

  2023cites this paper
• Hierarchical cue control of drug seeking in the face of cost

  2022cites this paper
• Modulation of methamphetamine memory reconsolidation by neural projection from basolateral amygdala to nucleus accumbens

  2022influential citation
• Infralimbic Projections to the Nucleus Accumbens Shell and Amygdala Regulate the Encoding of Cocaine Extinction Learning

  2022cites this paper
• Optogenetic activation of basolateral amygdala-to-nucleus accumbens core neurons promotes Pavlovian approach responses but not instrumental pursuit of reward cues.

  2022cites this paper
• The medial orbitofrontal cortex governs reward-related circuits in an age-dependent manner.

  2022cites this paper
• Optogenetic activation of basolateral amygdala projections to nucleus accumbens core promotes cue-induced expectation of reward but not instrumental pursuit of cues

  2021cites this paper
• Advances in understanding meso‐cortico‐limbic‐striatal systems mediating risky reward seeking

  2021cites this paper
• Negative Urgency Exacerbates Relapse to Cocaine Seeking After Abstinence.

  2021cites this paper
• Female rats display higher methamphetamine-primed reinstatement and c-Fos immunoreactivity than male rats.

  2021cites this paper
• The VTA-BLA-NAc circuit for sex reward inhibited by VTA GABAergic neurons under stress in male mice

  2021influential citation
• Reactivating a positive feedback loop VTA-BLA-NAc circuit associated with positive experience ameliorates the attenuated reward sensitivity induced by chronic stress

  2021influential citation
• Choose Your Path: Divergent Basolateral Amygdala Efferents Differentially Mediate Incentive Motivation, Flexibility and Decision-Making.

  2021cites this paper
• Bidirectional control of infant rat social behavior via dopaminergic innervation of the basolateral amygdala.

  2021cites this paper
• Maladaptive cue-controlled cocaine-seeking habits promote increased relapse severity in rats

  2021cites this paper
• Memory enhancing effects of nicotine, cocaine, and their conditioned stimuli; effects of beta-adrenergic and dopamine D2 receptor antagonists

  2021cites this paper
• Cocaine-Induced Projection- and Cell Type-Specific Adaptations in the Nucleus Accumbens

  2021cites this paper
• Neurochemical substrates linked to impulsive and compulsive phenotypes in addiction: A preclinical perspective

  2021cites this paper
• Astrocytes in Addictive Disorders.

  2021cites this paper
• Amygdalar κ-opioid receptor-dependent upregulating glutamate transporter 1 mediates depressive-like behaviors of opioid abstinence.

  2021cites this paper
• Psychostimulants

  2020cites this paper
• Basolateral Amygdala to Nucleus Accumbens Communication Differentially Mediates Devaluation Sensitivity of Sign- and Goal-Tracking Rats

  2020cites this paper
• Dopamine D1 receptor in the NAc shell is involved in delayed emergence from isoflurane anesthesia in aged mice

  2020cites this paper
• Targeting drug memory reconsolidation: a neural analysis.

  2020cites this paper
• The Basolateral amygdala → Nucleus Accumbens core circuit mediates the conditioned reinforcing effects of cocaine-paired cues on cocaine seeking

  2020influential citation
• Basolateral amygdala to nucleus accumbens projections differentially mediate flexibility of sign- and goal-tracking rats

  2020cites this paper
• Neural Substrates and Circuits of Drug Addiction.

  2020cites this paper
• The transition to compulsion in addiction

  2020cites this paper
• Reward-related dynamical coupling between basolateral amygdala and nucleus accumbens

  2020cites this paper
• Neuronal diversity of the amygdala and the bed nucleus of the stria terminalis.

  2020cites this paper
• Psychostimulant-Induced Adaptations in Nucleus Accumbens Glutamatergic Transmission.

  2020cites this paper
• Improving translation of animal models of addiction and relapse by reverse translation

  2020cites this paper
• Improving translation of animal models of addiction and relapse by reverse translation

  2020cites this paper
• Differences in the dopaminergic reward system in rats that passively and actively behave in the Porsolt test

  2019cites this paper
• A Critical Role of Basolateral Amygdala-to-Nucleus Accumbens Projection in Sleep Regulation of Reward Seeking.

  2019cites this paper
• Glutamatergic Neuroplasticity in Addiction

  2019cites this paper
• Therapeutic efficacy of environmental enrichment for substance use disorders.

  2019cites this paper
• Neurobiological theories of addiction

  2019cites this paper
• 2 Animal Models of Drug Addiction

  2018cites this paper
• Chemogenetic activation of the perirhinal cortex reverses methamphetamine-induced memory deficits and reduces relapse

  2018cites this paper
• Effects of Cocaine Self-Administration and Its Extinction on the Rat Brain Cannabinoid CB1 and CB2 Receptors

  2018cites this paper
• Posttraumatic Stress Disorder: From Neurobiology to Cycles of Violence

  2018cites this paper
• [18F]fallypride characterization of striatal and extrastriatal D2/3 receptors in Parkinson's disease

  2018cites this paper
• Role of glutamatergic system and mesocorticolimbic circuits in alcohol dependence.

  2018cites this paper
• Basolateral amygdala, nicotinic cholinergic receptors, and nicotine: Pharmacological effects and addiction in animal models and humans

  2018cites this paper
• Arc and homer 1a expression following intravenous administration of heroin and cocaine : a novel application of the catFISH technique

  2018cites this paper
• Corrélats psychobiologiques des variations individuelles dans le contrôle de la recherche de drogue par la nicotine et les indices environnementaux associés à la nicotine

  2018cites this paper
• Learning in alcohol dependence Pavlovian-to-instrumental transfer in alcohol dependence and relapse risk

  2018cites this paper
• Addictive behaviour in experimental animals: prospects for translation

  2018cites this paper
• Cellular basis of the intrastriatal functional shifts that underlie the development of habits: relevance for drug addiction

  2017cites this paper
• AMPK signaling in the nucleus accumbens core mediates cue-induced reinstatement of cocaine seeking

  2017cites this paper
• Are Cocaine-Seeking “Habits” Necessary for the Development of Addiction-Like Behavior in Rats?

  2017influential citation
• Optogenetics to Study Reward Learning and Addiction

  2017cites this paper
• Nucleus accumbens feedforward inhibition circuit promotes cocaine self-administration

  2017cites this paper
• Memory Systems of the Basal Ganglia

  2017cites this paper
• Basolateral amygdala and stress-induced hyperexcitability affect motivated behaviors and addiction

  2017cites this paper
• Effect of Novel Allosteric Modulators of Metabotropic Glutamate Receptors on Drug Self-administration and Relapse: A Review of Preclinical Studies and Their Clinical Implications.

  2017cites this paper
• Enhanced incentive motivation in obesity-prone rats is mediated by NAc core CP-AMPARs

  2017cites this paper
• Habit Learning and Addiction

  2017cites this paper
• Evaluation of glutamatergic treatment in reducing nicotine seeking behavior in rats

  2017cites this paper
• Impulse Control Disorders and Related Complications of Parkinson's Disease Therapy

  2017cites this paper
• Understanding Mood Disorders Using Electrophysiology and Circuit Breaking

  2017cites this paper
• Drug Cues, Conditioned Reinforcement, and Drug Seeking: The Sequelae of a Collaborative Venture With Athina Markou.

  2017cites this paper
• Adolescent Alcohol Drinking Renders Adult Drinking BLA-Dependent: BLA Hyper-Activity as Contributor to Comorbid Alcohol Use Disorder and Anxiety Disorders

  2017cites this paper
• The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis

  2016cites this paper
• Alcohol Cues, Craving, and Relapse: Insights from Animal Models

  2016cites this paper
• Bridging the Gap: Towards a cell-type specific understanding of neural circuits underlying fear behaviors

  2016cites this paper
• Transitionality in addiction: A "temporal continuum" hypotheses involving the aberrant motivation, the hedonic dysregulation, and the aberrant learning.

  2016cites this paper
• Severity of dependence modulates smokers’ functional connectivity in the reward circuit: a preliminary study

  2016cites this paper
• Optogenetic inhibition of cortical afferents in the nucleus accumbens simultaneously prevents cue-induced transient synaptic potentiation and cocaine-seeking behavior

  2016cites this paper
• Brain SEEKING Circuitry in Neuroeconomics: A Unifying Hypothesis for the Role of Dopamine-Energized Arousal of the Medial Forebrain Bundle in Enthusiasm-Guiding Decision-Making

  2016cites this paper
• Amygdala-ventral striatum circuit activation decreases long-term fear

  2016cites this paper
• Examination of methamphetamine reinstatement in female and male rats: A pre-clinical model of relapse

  2016cites this paper
• AMPA Receptor Plasticity in Accumbens Core Contributes to Incubation of Methamphetamine Craving.

  2016cites this paper
• Examination of Methamphetamine Reinstatement in Female and Male Rats: A Pre-Clinical Model of Relapse

  2016cites this paper
• Contribution of Noradrenaline, Serotonin, and the Basolateral Amygdala to Alcohol Addiction: Implications for Novel Pharmacotherapies for AUDs

  2016cites this paper
• How Preclinical Models Evolved to Resemble the Diagnostic Criteria of Drug Addiction.

  2016cites this paper