Background
We and others reported time-dependent increases in cue-induced cocaine seeking after
withdrawal, suggesting that craving incubates over time. Recently, we found that central
amygdala extracellular signal-regulated kinases (ERK) and glutamate are involved in
this incubation. Here, we further explored the role of central amygdala glutamate
in the incubation of cocaine craving by determining the effect of systemic or central
amygdala injections of the mGluR2/3 agonist LY379268 (which decreases glutamate release) on cue-induced cocaine seeking
during early and late withdrawal.
Methods
Rats were trained to self-administer cocaine for 10 days (6 hours/day); infusions
were paired with a tone-light cue. Cocaine seeking and craving after systemic or central
amygdala injections of LY379268 were then assessed in extinction tests in the presence
of the cocaine-associated cues during early (day 3) or late (day 21) withdrawal.
Results
Systemic (1.5 or 3 mg/kg) or central amygdala (.5 or 1.0 μg/side) injections of LY379268
attenuated enhanced extinction responding on day 21 but had no effect on lower extinction
responding on day 3.
Conclusions
Results confirm our previous findings on the role of central amygdala glutamate in
the incubation of cocaine craving and together with previous reports suggest that
mGluR2/3 agonists should be considered in the treatment of drug relapse.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Biological PsychiatryAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Molecular psychology: Roles for the ERK MAP kinase cascade in memory.Annu Rev Pharmacol Toxicol. 2002; 42: 135-163
- Effects of SCH-23390 infused into the amygdala or adjacent cortex and basal ganglia on cocaine seeking and self-administration in rats.Neuropsychopharmacology. 2006; 31: 363-374
- Metabotropic glutamate receptors: Electrophysiological properties and role in plasticity.Brain Res Rev. 1999; 29: 83-120
- The origin and neuronal function of in vivo nonsynaptic glutamate.J Neurosci. 2002; 22: 9134-9141
- Preferential effects of the metabotropic glutamate 2/3 receptor agonist LY379268 on conditioned reinstatement versus primary reinforcement: Comparison between cocaine and a potent conventional reinforcer.J Neurosci. 2004; 24: 4723-4727
- The ventral hippocampus and fear conditioning in rats.Exp Brain Res. 2001; 139: 39-52
- Regulation of ERK (extracellular signal regulated kinase), part of the neurotrophin signal transduction cascade, in the rat mesolimbic dopamine system by chronic exposure to morphine or cocaine.J Neurosci. 1996; 16: 4707-4715
- The novel mGluR2/3 agonist LY379268 attenuates cue-induced reinstatement of heroin seeking.Neuroreport. 2005; 16: 1013-1016
- Neurobiology of relapse to heroin and cocaine seeking: An update and clinical implications.Eur J Pharmacol. 2005; 526: 36-50
Bossert JM, Gray SM, Lu L, Shaham Y (2006): Activation of group II metabotropic glutamate receptors in the nucleus accumbens shell attenuates context-induced relapse of heroin seeking. Neuropsychopharmacology in press.
Bossert JM, Gray SM, Lu L, Shaham Y (in press): Activation of group II metabotropic glutamate receptors in the nucleus accumbens shell attenuates context-induced relapse of heroin seeking. Neuropsychopharmacology.
- Differential effects of excitotoxic lesions of the basolateral amygdala, ventral subiculum and medial prefrontal cortex on responding with conditioned reinforcement and locomotor activity potentiated by intra-accumbens infusions of D-amphetamine.Behav Brain Res. 1993; 55: 167-183
- Effects of the dopamine D-1 antagonist SCH 23390 microinjected into the accumbens, amygdala or striatum on cocaine self-administration in the rat.Brain Res. 1995; 692: 47-56
- Projections of the ventral subiculum to the amygdala, septum, and hypothalamus: A PHAL anterograde tract-tracing study in the rat.J Comp Neurol. 1992; 324: 180-194
- Cocaine-seeking behavior and AMPA receptor trafficking in the nucleus accumbens Soc Neurosci Abstr Program No. 1030.1. 2005
- Ventral subicular interaction with the hypothalamic paraventricular nucleus: Evidence for a relay in the bed nucleus of the stria terminalis.J Comp Neurol. 1993; 332: 1-20
- MK-801 reinstates drug-seeking behaviour in cocaine-trained rats.Neuroreport. 1998; 9: 637-640
- Conditioned reinforcing properties of stimuli paired with self-administered cocaine, heroin or sucrose: Implications for the persistence of addictive behaviour.Neuropharmacology. 2004; 47: 202-213
- Direct interactions between the basolateral amygdala and nucleus accumbens core underlie cocaine-seeking behavior by rats.J Neurosci. 2004; 24: 7167-7173
- The reinstatement model and relapse prevention: a clinical perspective.Psychopharmacology. 2003; 168: 31-41
- The neuropsychological basis of addictive behaviour.Brain Res Rev. 2001; 36: 129-138
- Associative processes in addiction and reward.Ann N Y Acad Sci. 1999; 877: 412-438
- Abstinence symptomatology and psychiatric diagnosis in cocaine abusers.Arch Gen Psychiatry. 1986; 43: 107-113
- Incubation of sucrose craving: effects of reduced training and sucrose pre-loading.Physiol Behav. 2005; 84: 73-79
- Incubation of cocaine craving after withdrawal.Nature. 2001; 412: 141-142
- Time-dependent increases in brain-derived neurotrophic factor protein levels within the mesolimbic dopamine system after withdrawal from cocaine: Implications for incubation of cocaine craving.J Neurosci. 2003; 23: 742-747
- Effect of the cocaine and sucrose withdrawal period on extinction behavior, cue-induced reinstatement and protein levels of the dopamine transporter and tyrosine hydroxylase in limbic and cortical areas in rats.Behav Pharmacol. 2002; 13: 379-388
- Cortical lesions: flavor illness and noise-shock conditioning.Behav Biol. 1974; 10: 173-181
- Novel pharmacotherapeutic approaches for the treatment of drug addiction and craving.Curr Opin Pharmacol. 2005; 5: 107-118
- Hippocampal pathway to the amygdala and stress ulcer development.Brain Res Bull. 1990; 25: 691-695
- Double dissociation of the effects of lesions of basolateral and central amygdala on conditioned stimulus-potentiated feeding and Pavlovian-instrumental transfer.Eur J Neurosci. 2003; 17: 1680-1894
- Impulsivity resulting from frontostriatal dysfunction in drug abuse: Implications for the control of behavior by reward-related stimuli.Psychopharamacology. 1999; 146: 373-390
- Glutamate systems in cocaine addiction.Curr Opin Pharmacol. 2004; 4: 23-29
- The ups and downs of addiction: role of metabotropic glutamate receptors.Trends Pharmacol Sci. 2004; 25: 265-272
- Different types of fear-conditioned behaviour mediated by separate nuclei within amygdala.Nature. 1997; 388: 377-380
- Activation of group II mGlu receptors blocks the enhanced drug taking induced by previous exposure to amphetamine.Eur J Neurosci. 2005; 21: 295-300
- The mGlu2/3 receptor agonist LY379268 blocks the expression of locomotor sensitization by amphetamine.Pharmacol Biochemi Behav. 2002; 73: 333-337
- “Incubation” of cocaine relapse during a disulfiram clinical trial.in: CPDD, Annual Meeting Abstracts. 2005: 90
- Differential contributions of the basolateral and central amygdala in the acquisition and expression of conditioned relapse to cocaine-seeking behavior.J Neurosci. 2001; 21: RC155
- A single infusion of brain-derived neurotrophic factor into the ventral tegmental area induces long-lasting potentiation of cocaine seeking after withdrawal.J Neurosci. 2004; 24: 1604-1611
- Cocaine seeking over extended withdrawal periods in rats: Different time courses of responding induced by cocaine cues versus cocaine priming over the first 6 months.Psychopharmacology. 2004; 176: 101-108
- Incubation of cocaine craving after withdrawal: A review of preclinical data.Neuropharmacology. 2004; 47: 214-226
- Central amygdala ERK signaling pathway is critical to incubation of cocaine craving.Nat Neurosci. 2005; 8: 212-219
- Mitogen-activated protein kinases in cell-cycle control.Cell Biochem Biophys. 2005; 43: 451-461
- Cocaine-induced CREB phosphorylation in nucleus accumbens of cocaine-sensitized rats is enabled by enhanced activation of extracellular signal-related kinase, but not protein kinase A.J Neurochem. 2005; 95: 1481-1494
- Conditioned cued recovery of responding following prolonged withdrawal from self-administered cocaine in rats: An animal model of relapse.Behav Pharmacol. 1996; 7: 754-763
- From motivation to action: Functional interface between the limbic system and the motor system.Prog Neurobiol. 1980; 14: 69-97
- Contribution of ventrolateral prefrontal cortex to the acquisition and extinction of conditioned fear in rats.Neurobiol Learn Mem. 1999; 72: 244-251
- Fos protein expression and cocaine-seeking behavior in rats after exposure to a cocaine self-administration environment.J Neurosci. 2000; 20: 798-805
- Molecular basis of long-term plasticity underlying addiction.Nat Rev Neurosci. 2001; 2: 119-128
- Classical conditioning in drug dependent humans.Ann N Y Acad Sci. 1992; 654: 400-415
- Distribution of a metabotropic glutamate receptor, mGluR2, in the central nervous system of the rat and mouse: An immunohistochemical study with a monoclonal antibody.Neurosci Res. 1998; 30: 65-82
- Connections of the amygdala of the rat.J Comp Neurol. 1982; 205: 30-48
- Responses of amygdaloid central nucleus neurons to stimulation of the insular cortex in awake rabbits.Neuroscience. 1987; 21: 471-485
- The Rat Brain in Stereotaxic Coordinates. 5 ed. Elsevier Academic Press, Amsterdam2005
- The glutamate hypothesis of reinforcement learning.Prog Brain Res. 2000; 126: 231-253
- The group II metabotropic glutamate receptor agonist, LY379268, inhibits both cocaine- and food-seeking behavior in rats.Psychopharmaocology. 2006; 186 (Berl): 143-149
- The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations.Neuroscience. 1996; 71: 949-976
- Connectivity of the rat amygaloid complex.in: Aggleton J.P. The Amygdala: A Functional Analysis. Oxford University Press, Oxford2000: 31-115
- Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons.J Neurosci. 2003; 23: 8800-8807
- Specificity in the projections of prefrontal and insular cortex to ventral striatopallidum and the extended amygdala.J Neurosci. 2005; 25: 11757-11767
- Effects of excitotoxic lesions of the central amygdaloid nucleus on the potentiation of reward-related stimuli by intra-accumbens amphetamine.Behav Neurosci. 1996; 110: 981-990
Rodd ZA, McKinzie DL, Bell RL, McQueen VK, Murphy JM, Schoepp DD, McBride WJ (in press): The metabotropic glutamate 2/3 receptor agonist LY404039 reduces alcohol-seeking but not alcohol self-administration in alcohol-preferring (P) rats. Behav Brain Res.
- The ventral hippocampus supports a memory representation of context and contextual fear conditioning: Implications for a unitary function of the hippocampus.Behav Neurosci. 2005; 119 (p): 154-163
- Rate-dependent effects of drugs: A review of the literature.Pharmacol Biochem Behav. 1976; 4: 73-83
- Unveiling the functions of presynaptic metabotropic glutamate receptors in the central nervous system.J Pharmacol Exp Ther. 2001; 299: 12-20
- Drug addiction, relapse, and the amygdala.Ann N Y Acad Sci. 2003; 985: 294-307
- Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior.Psychopharmacology. 2001; 154: 301-310
- Relapse to drug-seeking: neural and molecular mechanisms.Drug Alcohol Depend. 1998; 51: 49-69
- Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats.J Neurosci. 1997; 17: 2605-2614
- The reinstatement model of drug relapse: History, methodology and major findings.Psychopharmacology. 2003; 168: 3-20
- Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats.Psychopharmacology. 2001; 156: 98-107
- The anxiogenic drug yohimbine reinstates methamphetamine seeking in a rat model of drug relapse.Biol Psychiatry. 2004; 55: 1082-1089
- The contribution of drug history and time since termination of drug taking to footshock stress-induced cocaine seeking in rats.Psychopharmacology. 2005; 183: 210-217
- Reinstatement of drug-taking behavior as a method of assessing incentive motivational properties of drugs.in: Bozarth M.A. Methods of Assessing the Reinforcing Properties of Abused Drugs. Springer-Verlag, New York1987: 211-227
- What is the amygdala?.Trends Neurosci. 1998; 21: 323-331
- Neurochemical correlates of relapse to d-amphetamine self-administration by rats induced by stimulation of the ventral subiculum.Psychopharmacology. 2003; 168 (Berl): 99-108
- Distribution of metabotropic glutamate receptor mGluR3 in the mouse CNS: Differential location relative to pre- and postsynaptic sites.Neuroscience. 2001; 106: 481-503
- Inhibition of ERK pathway or protein synthesis during reexposure to drugs of abuse erases previously learned place preference.Proc Natl Acad Sci U S A. 2006; 103: 2932-2937
- Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties.J Neurosci. 2000; 20: 8701-8709
- Relapse to cocaine-seeking after hippocampal theta burst stimulation.Science. 2001; 292: 1175-1178
- Neurobiology of craving, conditioned reward and relapse.Curr Opin Pharmacol. 2005; 5: 9-19
- Addictive drugs as reinforcers: Multiple partial actions on memory systems.Addiction. 1996; 91 (discussion 951–965): 921-949
- The neurobiology of craving: Implications for the understanding and treatment of addiction.J Abnorm Psychol. 1988; 97: 118-132
- The extracellular signal-regulated kinase: Multiple substrates regulate diverse cellular functions.Growth Factors. 2006; 24: 21-44
- Extent of the tetrodotoxin induced blockade examined by pupillary paralysis elicited by intracerebral injection of the drug.Exp Brain Res. 1991; 83: 687-690
Article info
Publication history
Published online: August 10, 2006
Accepted:
April 17,
2006
Received in revised form:
April 13,
2006
Received:
March 13,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
