Abstract
Rationale
Recent studies have attempted to identify the neuroanatomical substrates underlying primed reinstatement of drug-seeking behavior. Identification of neuronal substrates will provide a logical rationale for designing pharmacological interventions in treating drug relapse.
Objective
The objective was to identify brain circuitry that is shared between cue-, drug- and stress-primed reinstatement, as well as identifying aspects of brain circuitry that are distinct for each stimulus modality. The resulting circuit offers theoretical interpretations for consideration in future studies.
Results
Aspects of the circuitry mediating reinstatement can be identified with reasonable confidence. The role of the basolateral amygdala in cue-primed reinstatement, the role of the ventral tegmental area in drug-primed reinstatement and the role of adrenergic innervation of the extended amygdala in stress-primed reinstatement are well characterized. Also, all three modes for priming reinstatement may converge on the anterior cingulate cortex and have a final common output through the core of the nucleus accumbens. Lacunae in our understanding of the circuit were identified, especially with regard to how stress priming is conveyed from the extended amygdala to the shared anterior cingulate accumbens core circuit.
Conclusions
The proposed convergence of priming stimuli into the glutamatergic projection from anterior cingulate to the accumbens core combined with the changes in glutamate transmission and signaling that accompany repeated psychostimulant administration points to the potential value of pharmacological agents that manipulate glutamate release or postsynaptic glutamate receptor signaling and trafficking in treating primed relapse in addicts.
Similar content being viewed by others
References
Ahmed SH, Koob GF (1997) Cocaine- but not food-seeking behavior is reinstated by stress after extinction. Psychopharmacology 132:289–295
Anderson SM, Bari AA, Pierce RC (2003) Administration of the D1-like dopamine receptor antagonist SCH-23390 into the medial nucleus accumbens shell attenuates cocaine priming-induced reinstatement of drug-seeking behavior in rats. Psychopharmacology DOI 10.1007/s00213-002-1298-5
Aston-Jones G, Delfs JM, Druhan J, Zhu Y (1999) The bed nucleus of the stria terminalis. A target site for noradrenergic actions in opiate withdrawal. Ann NY Acad Sci 877:486–498
Bechara A, Dolan S, Denburg N, Hindes A, Anderson SW, Nathan PE (2001) Decision-making deficits linked to a dysfunctional ventromedial prefrontal cortex revealed in alcohol and stimulant abusers. Neuropsychologia 39:376–389
Bonson KR, Grant SJ, Contoreggi CS, Links JM, Metcalfe J, Weyl HL, Kurian V, Ernst M, London ED (2002) Neural systems and cue-induced cocaine craving. Neuropsychopharmacology 26:376–386
Bradberry CW, Barrett-Larimore RL, Jatlow P, Rubino SR (2000) Impact of self-administered cocaine and cocaine cues on extracellular dopamine in mesolimbic and sensorimotor striatum in rhesus monkeys. J Neurosci 20:3874–3883
Breiter HC, Gollub RL, Weisskoff RM, Kennedy DN, Makris N, Berke JD, Goodman JM, Kantor HL, Gastfriend DR, Riorden JP, Mathew RT, Rosen BR, Hyman SE (1997) Acute effects of cocaine on human brain activity and emotion. Neuron 19:591–611
Capriles N, Amir S, Stewart J (2001) Inactivation of the prefrontal and orbitofrontal regions by tetrodotoxin attenuates stress-induced reinstatement of cocaine-seeking. Soc Neurosci Abstr 27:442.2
Carelli RM (2002) Nucleus accumbens cell firing during goal-directed behaviors for cocaine vs 'natural' reinforcement. Physiol Behav 76:379–387
Carelli RM, Ijames S (2000) Nucleus accumbens cell firing during maintenance, extinction, and reinstatement of cocaine self-administration behavior in rats. Brain Res 866:44–54
Carelli RM, Ijames SG (2001) Selective activation of accumbens neurons by cocaine-associated stimuli during a water/cocaine multiple schedule. Brain Res 907:156–161
Carr DB, Sesack SR (2000) GABA-containing neurons in the rat ventral tegmental area project to the prefrontal cortex. Synapse 38:114–123
Carroll R, Beattie E, von Zastrow M, Malenka R (2001) Role of AMPA receptor endocytosis in synaptic plasticity. Nat Rev Neurosci 2:315–324
Chang JY, Janak PH, Woodward DJ (2000) Neuronal and behavioral correlations in the medial prefrontal cortex and nucleus accumbens during cocaine self-administration by rats. Neuroscience 99:433–443
Childress AR, Mozley PD, McElgin W, Fitzgerald J, Reivich M, O'Brien CP (1999) Limbic activation during cue-induced cocaine craving. Am J Psychiatry 156:11–18
Churchill L, Zahm DS, Kalivas PW (1996) The mediodorsal nucleus of the thalamus. I. Forebrain GABAergic innervation. Neuroscience 70:93–102
Ciccocioppo R, Sanna PP, Weiss F (2001) Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: reversal by D(1) antagonists. Proc Natl Acad Sci USA 98:1976–1981
Cornish J, Kalivas P (2000) Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J Neurosci 20:RC89
Cornish JL, Duffy P, Kalivas PW (1999) A role of nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior. Neuroscience 93:1359–1368
Crespo JA, Manzanares J, Oliva JM, Corchero J, Palomo T, Ambrosio E (2001) Extinction of cocaine self-administration produces a differential time-related regulation of proenkephalin gene expression in rat brain. Neuropsychopharmacology 25:185–194
Daglish M, Weinstein A, Malizia A, Wilson S, Melichar J, Britten S, Brewer C, Lingford-Hughes A, Myles J, Graspy P, Nutt D (2001) Changes in regional cerebral blood flow elicited by craving memories in abstinent opiate-dependent subjects. Am J Psychiatry 158:1680–1686
De Vries TJ, Schoffelmeer AN, Binnekade R, Mulder AH, Vanderschuren LJ (1998) Drug-induced reinstatement of heroin- and cocaine-seeking behavior following long-term extinction is associated with expression of behavioral sensitization. Eur J Neurosci 10:3565–3571
de Wit H, Stewart J (1981) Reinstatement of cocaine-reinforced responding in the rat. Psychopharmacology 75:134–143
Di Ciano P, Everitt BJ (2001) Dissociable effects of antagonism of NMDA and AMPA/KA receptors in the nucleus accumbens core and shell on cocaine-seeking behavior. Neuropsychopharmacology 25:341–360
Di Ciano P, Blaha CD, Phillips AG (2001) Changes in dopamine efflux associated with extinction, CS-induced and d-amphetamine-induced reinstatement of drug-seeking behavior by rats. Behav Brain Res 120:147–158
Drummond DC, Litten RZ, Lowman C, Hunt WA (2000) Craving research: future directions. Addiction 95:S247–S255
Erb S, Stewart J (1999) A role for the bed nucleus of the stria terminalis, but not the amygdala in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking. J Neurosci 19:RC35
Erb S, Salmaso N, Rodaros D, Stewart J (2001) A role for the CRF-containing pathway from central nucleus of the amygdala to bed nucleus of the stria terminalis in the stress-induced reinstatement of cocaine seeking in rats. Psychopharmacology 158:360–365
Everitt BJ, Parkinson JA, Olmstead MC, Arroyo M, Robledo P, Robbins TW (1999) Associative processes in addiction and reward. The role of amygdala-ventral striatal subsystems. Ann NY Acad Sci 877:412–438
Fallon JH, Moore RY (1978) Catecholamine innervation of basal forebrain. IV. Topography of the dopamine projection to the basal forebrain and striatum. J Comp Neurol 180:545–580
Fuchs RA, See RE (2002) Basolateral amygdala inactivation abolishes conditioned stimulus- and heroin-induced reinstatement of extinguished heroin-seeking behavior in rats. Psychopharmacology 160:425–433
Fuchs RA, Tran-Nguyen LTL, Specio SE, Groff RS, Neisewander JL (1998) Predictive validity of the extinction/reinstatement model of drug craving. Psychopharmacology 135:151–160
Gaffan D, Murray EA (1990) Amygdalar interaction with the mediodorsal nucleus of the thalamus and the ventromedial prefrontal cortex in stimulus-reward associative learning in the monkey. J Neurosci 8:3144–3150
Garavan H, Pankiewicz J, Bloom A, Cho JK, Sperry L, Ross TJ, Salmeron BJ, Risinger R, Kelley D, Stein EA (2000) Cue-induced cocaine craving: neuroanatomical specificity for drug users and drug stimuli. Am J Psychiatry 157:1789–1798
George MS, Anton RF, Bloomer C, Teneback C, Drobes DJ, Lorberbaum JP, Nahas Z, Vincent DJ (2001) Activation of prefrontal cortex and anterior thalamus in alcoholic subjects on exposure to alcohol-specific cues. Arch Gen Psychiatry 58:345–352
Georges F, Aston-Jones G (2002) Activation of ventral tegmental area cells by the bed nucleus of the stria terminalis: a novel excitatory amino acid input to midbrain dopamine neurons. J Neurosci 22:5173–5187
Gerasimov MR, Schiffer WK, Gardner EL, Marsteller DA, Lennon IC, Taylor SJ, Brodie JD, Ashby CR Jr, Dewey SL (2001) GABAergic blockade of cocaine-associated cue-induced increases in nucleus accumbens dopamine. Eur J Pharmacol 414:205–209
Goto Y, O'Donnell P (2001) Network synchrony in the nucleus accumbens in vivo. J Neurosci 21:4498–5004
Grant S, London ED, Newlin DB, Villemagne VL, Liu X, Contoreggi C, Phillips RL, Kimes AS, Margolin A (1996) Activation of memory circuits during cue-elicited cocaine craving. Proc Natl Acad Sci USA 93:12040–12045
Grimm J, See R (2000) Dissociation of primary and secondary reward-relevant limbic nuclei in an animal model of relapse. Neuropsychopharmacology 22:473–479
Grimm JW, Kruzich PJ, See RE (2000) Contingent access to stimuli associated with cocaine self-administration is required for reinstatement of drug-seeking behavior. Psychobiology 28:383–386
Grimm JW, Hope BT, Wise RA, Shaham Y (2001) Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature 412:141–142
Groenewegen HJ (1988) Organization of afferent connections of the mediodorsal thalamic nucleus in the rat, related to mediodorsal-prefrontal topography. Neuroscience 24:379–431
Groenewegen HJ, Berendse HW, Wolters JG, Lohman AH (1990) The anatomical relationship of the prefrontal cortex with the striatopallidal system, the thalamus and the amygdala: evidence for a parallel organization. Prog Brain Res 85:95–116
Heimer L, Alheid GF, Zahm DS (1993) Basal forebrain organization: an anatomical framework for motor aspects of drive and motivation. In: Kalivas PW, Barnes CD (eds) Limbic motor circuits and neuropsychiatry. CRC Press, Boca Raton, pp 1–32
Henry DJ, White FJ (1995) The persistence of behavioral sensitization to cocaine parallels enhanced inhibition of nucleus accumbens neurons. J Neurosci 15:6287–6299
Hommer DW (1999) Functional imaging of craving. Alcohol Res Health 23:187–196
Hotsenpiller G, Giorgetti M, Wolf ME (2001) Alterations in behaviour and glutamate transmission following presentation of stimuli previously associated with cocaine exposure. Eur J Neurosci 14:1843–1855
Ito R, Dalley JW, Howes SR, Robbins TW, Everitt BJ (2000) Dissociation in conditioned dopamine release in the nucleus accumbens core and shell in response to cocaine cues and during cocaine-seeking behavior in rats. J Neurosci 20:7489–7495
Jentsch K, Taylor J (1999) Impulsivity resulting form frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology 146:373–390
Kalivas PW (2002) The development and expression of behavioral sensitization: temporal profile of changes in gene expression. In: Moldanado R (ed) Molecular biology of drug addiction. Humana Press, Totowa
Kalivas PW, Duffy P (1993) Time course of extracellular dopamine and behavioral sensitization to cocaine. I. Dopamine axon terminals. J Neurosci 13:266–275
Kalivas PW, Churchill L, Klitenick MA (1993) GABA and enkephalin projection from the nucleus accumbens and ventral pallidum to VTA. Neuroscience 57:1047–1060
Kantak KM, Black Y, Valencia E, Green-Jordan K, Eichembaum HB (2002) Dissociable effects of lidocaine inactivation of the rostral and caudal basolateral amygdala on the maintenance and reinstatement of cocaine-seeking behavior in rats. J Neurosci 22:1126–1136
Kilts CD, Schweitzer JB, Quinn CK, Gross RE, Muhammad F, Hofmann J, Drexler K (2001) Neural activity related to drug craving in cocaine addiction. Arch Gen Psychiatry 58:334–341
Koob GF, Robledo P, Markou A, Caine SB (1993) The mescorticolimbic circuit in drug dependence and reward—a role for the extended amygdala? In: Kalivas PW, Barnes CD (eds) Limbic motor circuits and neuropsychiatry. CRC Press, Roca Baton, pp 289–310
Kruzich PJ, See RE (2001) Differential contributions of the basolateral and central amygdala in the acquisition and expression of conditioned relapse to cocaine-seeking behavior. J Neurosci 21:RC155
Leri F, Flores J, Rodaros D, Stewart J (2002) Blockade of stress-induced but not cocaine-induced reinstatement by infusion of noradrenergic antagonists into the bed nucleus of the stria terminalis or the central nucleus of the amygdala. J Neurosci 22:5713–5718
London ED, Bonson KR, Ernst M, Grant S (1999) Brain imaging studies of cocaine abuse: implications for medication development. Crit Rev Neurobiol 13:227–242
Maas LC, Lukas SE, Kaufman MJ, Weiss RD, Daniels SL, Rogers VW, Kukes TJ, Renshaw PF (1998) Functional magnetic resonance imaging of human brain activation during cue-induced cocaine craving. Am J Psychiatry 155:124–126
McFarland K, Ettenberg A (1997) Reinstatement of drug-seeking behavior produced by heroin-predictive environmental stimuli. Psychopharmacology 131:86–92
McFarland K, Kalivas PW (2001) The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 21:8655–8663
McFarland K, Lapish CC, Kalivas PW (2002) Cocaine-induced reinstatement of drug-seeking behavior depends upon activation of a glutamate projection from the prefrontal cortex to the nucleus accumbens. Soc Neurosci Abstr 28:897.12
Meil WM, See RE (1997) Lesions of the basolateral amygdala abolish the ability of drug-associated cues to reinstate responding during withdrawal from self-administered cocaine. Behav Brain Res 87:139–148
Mogenson GJ, Brudzynski SM, Wu M, Yang CR, Yim CCY (1993) From motivation to action: a review of dopaminergic regulation of limbic-nucleus accumbens-pedunculopontine nucleus circuitries involved in limbic-motor integration. In: Kalivas PW, Barnes CD (eds) Limbic motor circuits and neuropsychiatry. CRC Press, Boca Raton, pp 193–236
Neisewander JL, O'Dell LE, Tran-Nguyen LTL, Castaneda E, Fuchs RA (1996) Dopamine overflow in the nucleus accumbens during extinction and reinstatement of cocaine self-administration behavior. Neuropsychopharmacology 15:506–514
Neisewander JL, Baker DA, Fuchs RA, Tran-Nguyen LTL, Palmer A, Marshall JF (2000) Fos protein expression and cocaine seeking behavior in rats after exposure to a cocaine self-administration environment. J Neurosci 20:798–805
Nestler E (2001) Molecular basis of long-term plasticity underlying addiction. Nat Rev Neurosci 2:119–128
Nicola SM, Deadwyler SA (2000) Firing rate of nucleus accumbens neurons is dopamine-dependent and reflects the timing of cocaine-seeking behavior in rats on a progressive ratio schedule of reinforcement. J Neurosci 20:5526–5537
Nicola SM, Surmeier J, Malenka RC (2000) Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu Rev Neurosci 23:185–215
Oyoshi T, Nishijo H, Asakura T, Takamura Y, Ono T (1996) Emotional and behavioral correlates of mediodorsal thalamic neurons during associative learning in rats. J Neurosci 16:5812–5829
Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK, Pierce RC (2002) Cocaine administered into the medial prefrontal cortex reinstates cocaine-seeking behavior by increasing AMPA receptor-mediated glutamate transmission in the nucleus accumbens. J Neurosci 22:2916–2925
Peoples LL, West MO (1996) Phasic firing of single neurons in the rat nucleus accumbens correlated with the timing of intravenous cocaine self-administration. J Neurosci 16:3459–3473
Peoples LL, Uzwiak AJ, Gee F, West MO (1997) Operant behavior during sessions of intravenous cocaine infusion is necessary and sufficient for phasic firing of single nucleus accumbens neurons. Brain Res 757:280–284
Petry NM (2001) Substance abuse, pathological gambling and impulsiveness. Drug Alcohol Depend 63:29–38
Piazza PC, Le Moal M (1996) Pathophysiological basis of vulnerability to drug abuse: role of interreaction between stress, glucocorticoids and dopaminergic neurons. Annu Rev Pharmacol Toxicol 36:359–378
Pierce RC, Bell K, Duffy P, Kalivas PW (1996) Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J Neurosci 16:1550–1560
Reid MS, Berger SP (1996) Evidence for sensitization of cocaine-induced nucleus accumbens glutamate release. Neuroreport 7:1325–1329
Rogers RD, Everitt BJ, Baldacchino AM, Blackshaw AJ, Swainsona R, Bakera NB, Huntera J, Carthya T, Bookera E, London M, Deakin JFW, Sahakian GJ, Robbins TW (1999) Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monaminergic mechanisms. Neuropsychopharmacology 20:322–339
Schmidt EF, Sutton MA, Schad CA, Karanian DA, Brodkin ES, Self DW (2001) Extinction training regulated tyrosine hydroxylase during withdrawal from cocaine self-administration. J Neuroscience 21:RC137
Schultz W (1998) Predictive reward signal of dopamine neurons. Am J Physiol 80:1–27
See RE (2002) Neural substrates of conditioned-cued relapse to drug-seeking behavior. Pharmacol Biochem Behav 71:517–529
See RE, Kruzich PJ, Grimm JW (2001) Dopamine, but not glutamate, receptor blockade in the basolateral amygdala attenuates conditioned reward in a rat model of relapse to cocaine-seeking behavior. Psychopharmacology 154:301–310
Self DW, Genova LM, Hope BT, Barnhart WJ, Spencer JJ, Nestler EJ (1998) Involvement of cAMP-dependent protein kinase in the nucleus accumbens in cocaine self-administration and relapse of cocaine-seeking behavior. J Neurosci 18:1848–1859
Sell L, Morris J, Bearn J, Frackowiak R, Friston K, Dolan R (2000) Neural responses associated with cue evoked emotional states and heroin in opiate addicts. Drug Alcohol Depend 60:207–216
Shaham Y, Stewart J (1996) Effects of opioid and dopamine receptor antagonists on relapse induced by stress and re-exposure to heroin in rats. Psychopharmacology 125:385–391
Shaham Y, Funk D, Erb S, Brown TJ, Walker C-D, Stewart J (1997) Corticotropin-releasing factor, but not corticosterone, is involved in stress-induced relapse to heroin-seeking in rats. J Neurosci 17:2605–2614
Shaham Y, Erb S, Stewart J (2000a) Stress-induced drug seeking to heroin and cocaine in rats: a review. Brain Res Rev 33:13–33
Shaham Y, Highfield D, Delfs J, Leung S, Stewart J (2000b) Clonidine blocks stress-induced reinstatement of heroin seeking in rats: an effect independent of locus coeruleus noradrenergic neurons. Eur J Neurosci 12:292–302
Shalev U, Yap J, Shaham Y (2001) Leptin attenuates acute food deprivation-induced relapse to heroin seeking. J Neurosci 21:RC129
Shalev U, Grimm JW, Shaham Y (2002) Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54:1–42
Sorg BA, Davidson DL, Kalivas PW, Prasad BM (1997) Repeated daily cocaine alters subsequent cocaine-induced increase of extracellular dopamine in the medial prefrontal cortex. J Pharmacol Exp Ther 281:54–61
Stewart J (1984) Reinstatement of heroin and cocaine self-administration behavior in the rat by intracerebral application of morphine in the ventral tegmental area. Pharmacol Biochem Behav 20:917–923
Stewart J, Vezina P (1988) A comparison of the effects of intra-accumbens injections of amphetamine and morphine on reinstatement of heroin intravenous self-administration. Brain Res 457:287–294
Sutton MA, Schmidt EF, Choi K-H, Schad CA, Whisler K, Simmons D, Karanian DA, Monteggia LM, Neve RL, Self DW (2003) Extinction-dependent plasticity in AMPA receptors regulates cocaine seeking. Nature 421:70–75
Swanson C, Baker D, Carson D, Worley P, Kalivas P (2001) Repeated cocaine administration attenuates group I metabotropic glutamate receptor-mediated glutamate release and behavioral activation: a potential role for Homer 1b/c. J Neurosci 21:9043–9052
Swanson LW (1982) The projections of the ventral tegmental area and adjacent regions: a combined fluorescent retrograde tracer and immunofluorescence study in the rat. Brain Res Bull 9:321–353
Thomas KL, Everitt BJ (2001) Limbic-cortical-ventral striatal activation during retrieval of a discrete cocaine-associated stimulus: a cellular imaging study with gamma protein kinase C expression. J Neurosci 21:2526–2535
Thomas KL, Laroche S, Errington ML, Bliss TVP, Hunt SP (1994) Spatial and temporal changes in signal transduction pathways during LTP. Neuron 13:737–745
Thomas MJ, Beurrier C, Bonci A, Malenka RC (2001) Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat Neurosci 4:1217–23
Tiffany ST, Carter BL (1998) Is craving the source of compulsive drug use? J Psychopharmacol 12:23–30
Tran-Nguyen LT, Fuchs RA, Coffey GP, Baker DA, O'Dell LE, Neisewander JL (1998) Time-dependent changes in cocaine-seeking behavior extracellular dopamine levels in the amygdala during cocaine withdrawal. Neuropsychopharmacology 19:48–59
Trantham H, Szumlinski K, McFarland K, Kalivas P, Lavin A (2002) Repeated cocaine administration alters the electrophysiological properties of prefrontal cortical neurons. Neuroscience 113:749
Volkow ND, Wang GJ, Fowler JS, Hitzemann R, Angrist B, Gatley SJ, Logan J, Ding YS, Pappas N (1999) Association of methylphenidate-induced craving with changes in right striato-orbitofrontal metabolism in cocaine abusers: implications in addiction. Am J Psychiatry 156:19–26
Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL (2001) Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292:1175–1178
Weiss F, Maldonado-Vlaar C, Parsons L, Kerr T, Smith D, Ben-Shahar O (2000) Control of cocaine-seeking behavior by drug associated stimuli in rats: effects on recovery of extinguished operant-responding and extracellular dopamine levels in the amygdala and nucleus accumbens. Proc Natl Acad Sci USA 97:4321–4326
Weissenborn R, Whitelaw RB, Robbins TW, Everitt BJ (1998) Excitotoxic lesions of the mediodorsal thalamic nucleus attenuate intravenous cocaine self-administration. Psychopharmacology 140:225–232
Wexler BE, Gottschalk CH, Fulbright RK, Prohovnik I, Lacadie CM, Rounsaville BJ, Gore JC (2001) Functional magnetic resonance imaging of cocaine craving. Am J Psychiatry 158:86–95
White FJ, Kalivas PW (1998) Neuroadaptations involved in amphetamine and cocaine addiction. Drug Alcohol Depend 51:141–154
Whitelaw RB, Markou A, Robbins TW, Everitt BJ (1996) Excitotoxic lesions of the basolateral amygdala impair the acquisition of cocaine-seeking behaviour under a second-order schedule of reinforcement. Psychopharmacology 127:213–224
Woodward DJ, Chang JY, Janak P, Azarov A, Anstrom K (2000) Activity patterns in mesolimbic regions in rats during operant tasks for reward. Prog Brain Res 126:303–322
Worley PF, Bhat RV, Baraban JM, Erickson CA, McNaughton BL, Barnes CM (1993) Thresholds for synaptic activation of transcription factors in the hippocampus: correlation with long-term enhancement. J Neurosci 13:4776–4786
Xi Z-X, Ramamoorthy S, Baker DA, She H, Devadoss JS, Kalivas PW (2002) Modulation of group II metabotropic glutamate receptor signaling by chronic cocaine. J Pharmacol Exp Ther 308:608–615
Zhang X-F, Hu X-T, White FJ (1998) Whole-cell plasticity in cocaine withdrawal: reduced sodium current in nucleus accumbens neurons. J Neurosci 18:488–498
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kalivas, P.W., McFarland, K. Brain circuitry and the reinstatement of cocaine-seeking behavior. Psychopharmacology 168, 44–56 (2003). https://doi.org/10.1007/s00213-003-1393-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00213-003-1393-2