Abstract
The effect of previous exposure to psychostimulants on the subsequent self-administration of cocaine as well as reinstatement of this behavior by priming infusions of AMPA into the nucleus accumbens (NAcc) was examined. Rats were exposed to five injections, one injection every third day, of either saline or amphetamine (AMPH: 1.5 mg/kg, i.p.). Starting 10 days later, they were trained to self-administer cocaine (0.3 mg/kg/infusion, i.v.) and subsequently tested under a progressive ratio (PR) schedule for 4 consecutive days. As expected, rats exposed to AMPH worked more and obtained more cocaine infusions than saline exposed controls on the PR test sessions. Following daily extinction sessions during which saline was substituted for cocaine, the effect of priming infusions of AMPA (0.0, 0.08, or 0.8 nmol/0.5 μl/side) into the NAcc was then examined on two tests: one conducted 4 days after the last cocaine PR test session (2–3 weeks after the last AMPH exposure injection) and the next 4 weeks later. Consistent with previous reports, NAcc AMPA dose-dependently reinstated cocaine seeking on both tests regardless of exposure condition. Importantly, this priming effect of NAcc AMPA was significantly enhanced in AMPH compared to saline exposed rats on the first test conducted 2–3 weeks after AMPH. On the second test, conducted 4 weeks after cocaine, reinstatement was similarly enhanced in both groups to levels observed on the first test in AMPH exposed rats. These results indicate that both noncontingent (AMPH) and contingent (cocaine) exposure to psychostimulants enhances the reinstatement of cocaine seeking by NAcc AMPA and appears to do so in a time-dependent manner.
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References
Banke TG, Bowie D, Lee HK, Huganir RL, Schousboe A, Traynelis SF (2000). Control of GluR1 AMPA receptor function by cAMP-dependent protein kinase. J Neurosci 20: 89–102.
Bell K, Duffy P, Kalivas PW (2000). Context-specific enhancement of glutamate transmission by cocaine. Neuropsychopharmacology 23: 335–344.
Bell K, Kalivas PW (1996). Context-specific cross-sensitization between systemic cocaine and intra-accumbens AMPA infusion in the rat. Psychopharmacology 127: 377–383.
Benke TA, Luthi A, Isaac JTR, Collingridge GL (1998). Modulation of AMPA receptor unitary conductance by synaptic activity. Nature 393: 793–797.
Chao SZ, Ariano MA, Peterson DA, Wolf ME (2002). D1 dopamine receptor stimulation increases GluR1 surface expression in nucleus accumbens neurons. J Neurochem 83: 704–712.
Childress AR, Ehrman RN, Rohsenow D, Robbins SJ, O'Brien CP (1993). Classically conditioned factors in drug dependence. In: Lowinson J, Ruiz P, Millman R (eds). Comprehensive Textbook of Substance Abuse. Williams and Wilkins: Baltimore. pp 56–69.
Christie MJ, Summers RJ, Stephenson JA, Cook CJ, Beart PM (1987). Excitatory amino acid projections to the nucleus accumbens septi in the rat: a retrograde transport study utilizing D[3H]aspartate and [3H]GABA. Neuroscience 22: 425–439.
Churchill L, Swanson CJ, Urbina M, Kalivas PW (1999). Repeated cocaine alters glutamate receptor subunit levels in the nucleus accumbens and ventral tegmental area of rats that develop behavioral sensitization. J Neurochem 72: 2397–2403.
Cornish JL, Duffy P, Kalivas PW (1999). A role for nucleus accumbens glutamate transmission in the relapse to cocaine-seeking behavior. Neuroscience 93: 1359–1367.
Cornish JL, Kalivas PW (2000). Glutamate transmission in the nucleus accumbens mediates relapse in cocaine addiction. J Neurosci 20: RC89.
De Vries TJ, Schoffelmeer ANM, Binnekade R, Mulder AH, Vanderschuren LJMJ (1998). Drug-induced reinstatement of heroin- and cocaine-seeking behaviour following long-term extinction is associated with expression of behavioural sensitization. Eur J Neurosci. 10: 3565–3571.
De Vries TJ, Schoffelmeer ANM, Binnekade R, Raaso H, Vanderschuren LJMJ (2002). Relapse to cocaine- and heroin-seeking behavior mediated by dopamine D2 receptors is time-dependent and associated with behavioral sensitization. Neuropsychopharmacology 26: 18–26.
Derkach V, Barria A, Soderling TR (1999). Ca2+/calmodulin-kinase II enhances channel conductance of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate type glutamate receptors. Proc Natl Acad Sci 96: 3269–3274.
Deroche-Gamonet V, Martinez A, Le Moal M, Piazza PV (2003). Relationships between individual sensitivity to CS- and cocaine-induced reinstatement in the rat. Psychopharmacology 168: 201–207.
Di Chiara G (1995). The role of dopamine in drug abuse viewed from the perspective of its role in motivation. Drug Alcohol Depend 38: 95–137.
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.
Fitzgerald LW, Ortiz J, Hamedani AG, Nestler EJ (1996). Drugs of abuse and stress increase the expression of GluR1 and NMDAR1 glutamate receptor subunits in the rat ventral tegmental area: common adaptations among cross-sensitizing agents. J Neurosci 16: 274–282.
Ghasemzadeh MB, Nelson LC, Lu X-Y, Kalivas PW (1999). Neuroadaptations in ionotropic and metabotropic glutamate receptor mRNA produced by cocaine treatment. J Neurochem 72: 157–165.
Grimm JW, Hope BT, Wise RA, Shaham Y (2001). Neuroadaptation. Incubation of cocaine craving after withdrawal. Nature 412: 141–142.
Grimm JW, Lu L, Hayashi T, Hope BT, Su TP, Shaham Y (2003). 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 23: 742–747.
Grimm JW, See RE (2000). Dissociation of primary and secondary reward-relevant limbic nuclei in an animal model of relapse. Neuropsychopharmacology 22: 473–479.
Hayashi Y, Shi SH, Esteban JA, Piccini A, Poncer JC, Malinow R (2000). Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain intereaction. Science 287: 2262–2267.
Henry DJ, White FJ (1991). Repeated cocaine administration causes persistent enhancement of D1 dopamine receptor sensitivity within the rat nucleus accumbens. J Pharmacol Exp Ther 258: 882–890.
Hooks MS, Duffy P, Striplin C, Kalivas PW (1994). Behavioral and neurochemical sensitization following cocaine self-administration. Psychopharmacology 115: 265–272.
Jackson A, Mead AN, Rocha BA, Stephens DN (1998). AMPA receptors and motivation for drug: effect of the selective antagonist NBQX on behavioural sensitization and on self-administration in mice. Behav Pharmacol 9: 457–467.
Jaffe JH (1990). Drug addiction and drug abuse. In: Gilman AG, Rall TW, Nies AS, Taylor P (eds). Goodman and Gilman's The Pharmacological Basis of Therapeutics. Pergamon: New York. pp 522–573.
Jaffe JH, Cascella NG, Kumor KM, Sherer MA (1989). Cocaine-induced cocaine craving. Psychopharmacology 97: 59–64.
Karler R, Calder LD, Bedingfield JB (1994). Cocaine behavioral sensitization and the excitatory amino acids. Psychopharmacology 115: 305–310.
Karler R, Calder LD, Turkanis SA (1991). DNQX blockade of amphetamine behavioral sensitization. Brain Res 552: 295–300.
Koob GF, Sanna PP, Bloom FE (1998). Neuroscience and addiction. Neuron 21: 467–476.
Lee HKL, Barbarosie M, Kameyama K, Bear MF, Huganir RL (2000). Regulation of distinct AMPA receptor phosphorylation sites during bidirectional synaptic plasticity. Nature 405: 955–959.
Lee HKL, Takamiya K, Han JS, Man H, Kim CH, Rumbaugh G et al (2003). Phosphorylation of the AMPA receptor GluR1 subunit is required for synaptic plasticity and retention of spatial memory. Cell 112: 631–643.
Li Y, Vartanian AJ, White FJ, Xue CJ, Wolf ME (1997). Effects of the AMPA receptor antagonist NBQX on the development and expression of behavioral sensitization to cocaine and amphetamine. Psychopharmacology 134: 266–276.
Lorrain DS, Arnold GM, Vezina P (2000). Previous exposure to amphetamine increases incentive to obtain the drug: long-lasting effects revealed by the progressive ratio schedule. Behav Brain Res 107: 9–19.
Lu L, Grimm JW, Shaham Y, Hope BT (2003). Molecular neuroadaptations in the accumbens and ventral tegmental area during the first 90 days of forced abstinence from cocaine self-administration in rats. J Neurochem 85: 1604–1613.
Lu W, Chen H, Xue CJ, Wolf ME (1997). Repeated amphetamine administration alters the expression of mRNA for AMPA receptor subunits in rat nucleus accumbens and prefrontal cortex. Synapse 26: 269–280.
Lu W, Wolf ME (1999). Repeated amphetamine administration alters AMPA receptor subunit expression in rat nucleus accumbens and medial prefrontal cortex. Synapse 32: 119–131.
Mangiavacchi S, Wolf ME (2004). D1 dopamine receptor stimulation increases the rate of AMPA receptor insertion onto the surface of cultured nucleus accumbens neurons through a pathway dependent on protein kinase A. J Neurochem 88: 1261–1271.
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 (2003). Prefrontal glutamate release into the core of the nucleus accumbens mediates cocaine-induced reinstatement of drug-seeking behavior. J Neurosci 23: 3531–3537.
Mead AN, Stephens DN (1998). AMPA-receptors are involved in the expression of amphetamine-induced behavioural sensitization, but not in the expression of amphetamine-induced conditioned activity in mice. Neuropharmacology 37: 1131–1138.
Mendrek A, Blaha CD, Phillips AG (1998). Pre-exposure of rats to amphetamine sensitizes self-administration of this drug under a progressive ratio schedule. Psychopharmacology 135: 416–422.
Meredith GE, Pennartz CM, Groenewegen HJ (1993). The cellular framework for chemical signalling in the nucleus accumbens. Prog Brain Res 99: 3–24.
Park WK, Bari AA, Jey AR, Anderson SM, Spealman RD, Rowlett JK et al (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.
Paxinos G, Watson C (1997). The Rat Brain in Stereotaxic Coordinates: Compact, 3rd edn. Academic Press: San Diego, CA.
Pellegrino LJ, Pellegrino AS, Cushman AJ (1979). A Stereotaxic Atlas of the Rat Brain. Plenum Press: New York, NY.
Pennartz CMA, Kitai ST (1991). Hippocampal inputs to identified neurons in an in vitro slice preparation of the rat nucleus accumbens: evidence for feed-forward inhibition. J Neurosci 11: 2838–2847.
Phillips AG, Di Ciano P (1996). Behavioral sensitization is induced by intravenous self-administration of cocaine by rats. Psychopharmacology 124: 279–281.
Pierce RC, Bell K, Duffy P, Kalivas PW (1996a). Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J Neurosci 16: 1550–1560.
Pierce RC, Duffy P, Kalivas PW (1996b). Changes in excitatory amino acid transmission in the nucleus accumbens associated with behavioral sensitization to cocaine during early withdrawal. Neurosci Net article # 1996-008.
Pierre PJ, Vezina P (1997). Predisposition to self-administer amphetamine: the contribution of response to novelty and prior exposure to the drug. Psychopharmacology 129: 277–284.
Richardson NR, Roberts DC (1996). Progressive ratio schedules in drug self-administration studies in rats: a method to evaluate reinforcing efficacy. J Neurosci Methods 66: 1–11.
Scheggi S, Mangiavacchi S, Masi F, Gambarana C, Tagliamonte A, De Montis MG (2002). Dizocilpine infusion has a different effect in the development of morphine and cocaine sensitization: behavioral and neurochemical aspects. Neuroscience 109: 267–274.
Self DW, Barnhart WJ, Lehman DA, Nestler EJ (1996). Opposite modulation of cocaine-seeking behavior by D1- and D2-like dopamine receptor agonists. Science 271: 1586–1589.
Shalev U, Grimm JW, Shaham Y (2002). Neurobiology of relapse to heroin and cocaine seeking: a review. Pharmacol Rev 54: 1–42.
Suto N, Austin JD, Tanabe LM, Kramer MK, Wright DA, Vezina P (2002). Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in a D1 dopamine dependent manner. Neuropsychopharmacology 27: 970–979.
Suto N, Pham CT, Baker LK, Vezina P (2003b). Enhanced reinstatement of drug seeking by AMPA in amphetamine pre-exposed rats requires dopamine receptor activation in the nucleus accumbens. Soc Neurosci Abstr 29: 112.9 Manuscript submitted.
Suto N, Tanabe LM, Austin JD, Creekmore E, Vezina P (2003a). Previous exposure to VTA amphetamine enhances cocaine self-administration under a progressive ratio schedule in an NMDA, AMPA/kainate, and metabotropic glutamate receptor-dependent manner. Neuropsychopharmacology 28: 629–639.
Sutton MA, Schmidt EF, Choi KH, Schad CA, Whisler K, Simmons D et al (2003). Extinction-induced upregulation in AMPA receptors reduces cocaine-seeking behavior. Nature 421: 70–75.
Thomas MJ, Beurrier C, Bonci A, Malenka RC (2001). Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nature Neurosci 4: 1217–1223.
Tran-Nguyen LT, Fuchs RA, Coffey GP, Baker DA, O'Dell LE, Neisewander JL (1998). Time-dependent changes in cocaine-seeking behavior and extracellular dopamine levels in the amygdala during cocaine withdrawal. Neuropsychopharmacology 19: 48–59.
Tzschentke TM, Schmidt WJ (1997). Interactions of MK-801 and GYKI 52466 with morphine and amphetamine in place preference conditioning and behavioural sensitization. Behav Brain Res 84: 99–107.
Vanderschuren LJ, Kalivas PW (2000). Alterations in dopaminergic and glutamatergic transmission in the induction and expression of behavioral sensitization: a critical review of preclinical studies. Psychopharmacology 151: 99–120.
Vezina P (2004). Sensitization of midbrain dopamine neuron reactivity and the self-administration of psychomotor stimulant drugs. Neurosci Biobehav Rev 27: 827–839.
Vezina P, Lorrain DS, Arnold GM, Austin JD, Suto N (2002). Sensitization of midbrain dopamine neuron reactivity promotes the pursuit of amphetamine. J Neurosci 22: 4654–4662.
Vorel SR, Liu X, Hayes RJ, Spector JA, Gardner EL (2001). Relapse to cocaine-seeking after hippocampal theta burst stimulation. Science 292: 1175–1178.
Wise RA (1998). Drug-activation of brain reward pathways. Drug Alcohol Depend 51: 13–22.
Wise RA, Murray A, Bozarth MA (1990). Bromocriptine self-administration and bromocriptine reinstatement of cocaine-trained and heroin-trained lever pressing in rats. Psychopharmacology 100: 355–360.
Wolf ME, White FJ, Nassar R, Brooderson RJ, Khansa MR (1993). Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization. J Pharmacol Exp Ther 264: 249–255.
Zhang XF, Hu XT, White FJ (1998). Whole-cell plasticity in cocaine withdrawal: reduced sodium currents in nucleus accumbens neurons. J Neurosci 18: 488–498.
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This research was supported by grant DA-09397 (PV) from the USPHS.
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Suto, N., Tanabe, L., Austin, J. et al. Previous Exposure to Psychostimulants Enhances the Reinstatement of Cocaine Seeking by Nucleus Accumbens AMPA. Neuropsychopharmacol 29, 2149–2159 (2004). https://doi.org/10.1038/sj.npp.1300533
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DOI: https://doi.org/10.1038/sj.npp.1300533
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