Abstract
It is increasingly well accepted that addiction can be viewed as a form of neuronal plasticity, even as a type of very powerful, albeit maladaptive, learning. On a behavioral level, this can be conceptualized as the transition from experimentation to compulsive drug-seeking behavior. This view of addiction has been strengthened by many recent studies demonstrating commonalities between mechanisms underlying learning and addiction. Both are associated with changes in gene expression, phosphorylation and phosphatase cascades, neurotrophin signaling, altered dendritic morphology, and activity-dependent forms of plasticity such as long-term potentiation (LTP) and long-term depression (LTD) (1,2). Through these mechanisms, drugs of abuse are proposed to strengthen or weaken activity in pathways related to motivation and reward. This in turn may produce behavioral changes that drive compulsive drug-seeking behavior in addiction, including sensitization of incentive-motivational effects of drugs, enhanced ability of drug-conditioned stimuli to control behavior, and loss of inhibitory control mechanisms that normally govern reward-seeking behavior (3,4).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hyman, S. E. and Malenka, R. C. (2001) Addiction and the brain: the neurobiology of compulsion and its persistence. Nat. Rev. 2, 695ā703.
Wolf, M. E. (2002) Addiction and glutamate-dependent plasticity, in Glutamate and Addiction (Herman, B. H., Frankenheim, J., Litten, R., Sheridan, P. H., Weight, F. F., and Zukin, S. R., eds.), Humana Press, Totowa, NJ, pp. 127ā142.
Jentsch, J. D. and Taylor, J. R. (1999) Impulsivity resulting from frontostriatal dysfunction in drug abuse: implications for the control of behavior by reward-related stimuli. Psychopharmacology 146, 373ā390.
Everitt, B. J. and Wolf, M. E. (2002) Psychomotor stimulant addiction: a neural systems perspective. J. Neurosci. 22, 3312ā3320.
Wolf, M. E. (2001) The neuroplasticity of addiction, in Toward a Theory of Neuroplasticity (Shaw, C. A. and McEachern, J. C., eds.), Taylor & Francis, Philadelphia, pp. 359ā372.
Robinson, T. E. and Berridge, K. C. (1993) The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res. Rev. 18, 247ā291.
Robinson, T. E. and Berridge, K. C. (2000) The psychology and neurobiology of addiction: an incentive-sensitization view. Addiction 95 (Suppl. 2), S91āS117.
Wolf, M. E. (1998) The role of excitatory amino acids in behavioral sensitization to psychomotor stimulants. Prog. Neurobiol. 54, 679ā720.
White, F. J., Hu, X.-T., Zhang, X.-F., and Wolf, M. E. (1995) Repeated administration of cocaine or amphetamine alters neuronal responses to glutamate in the mesoaccumbens dopamine system. J. Pharmacol. Exp. Ther. 273, 445ā454.
Zhang, X.-F., Hu, X.-T., White, F. J., and Wolf, M. E. (1997) Increased responsiveness of ventral tegmental area dopamine neurons to glutamate after repeated administration of cocaine or amphetamine is transient and selectively involves AMPA receptors. J. Pharmacol. Exp. Ther. 281, 699ā706.
Giorgetti, M., Hotsenpiller, G., Ward, P., Teppen, T., and Wolf, M. E. (2001) Amphetamine-induced plasticity of AMPA receptors in the ventral tegmental area: effects on extracellular levels of dopamine and glutamate in freely moving rats. J. Neurosci.. 21, 6362ā6369.
Fitzgerald, L. W., Ortiz, J., Hamedani, A. G., and Nestler, E. J. (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, 274ā282.
Ortiz, J., Fitzgerald, L. W., Charlton, M., et al. (1995) Biochemical actions of chronic ethanol exposure in the mesolimbic dopamine system. Synapse 21, 289ā298.
Churchill, L., Swanson, C. J., Urbina, M., and Kalivas, P. W. (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, 2397ā2403.
Lu, W., Monteggia, L. M., and Wolf, M. E. (2002) Repeated administration of amphetamine or cocaine does not alter AMPA receptor subunit expression in the rat midbrain. Neuropsychopharmacology 26, 1ā13.
Carlezon, W. A., Jr., Boundy, V. A., Haile, C. N., et al. (1997) Sensitization to morphine induced by viral-mediated gene transfer. Science 277, 812ā814.
Carlezon, W. A., Jr., Haile, C. N., Coopersmith, R., et al. (2000) Distinct sites of opiate reward and aversion within the midbrain identified using a herpes simplex virus vector expressing GluR1. J. Neurosci. 20, RC62.
Ben-Shahar, O. and Ettenberg, A. (1994) Repeated stimulation of the ventral teg-mental area sensitizes the hyperlocomotor response to amphetamine. Pharmacol. Biochem. Behav. 48, 1005ā1009.
Schenk, S. and Snow, S. (1994) Sensitization to cocaineās motor activating properties produced by electrical kindling of the medial prefrontal cortex but not of the hippocampus. Brain Res. 659, 17ā22.
Steketee, J. D. and Kalivas, P. W. (1991) Sensitization to psychostimulants and stress after injection of pertussis toxin into the A10 dopamine region. J. Pharmacol. Exp. Ther. 259, 916ā924.
Bardo, M. T., Robinet, P. M., Mattingly, B. A., and Margulies, J. E. (2001) Effect of 6-hydroxydopamine or repeated amphetamine treatment on mesencephalic mRNA levels for AMPA glutamate receptor subunits in the rat. Neurosci. Lett. 302, 133ā136.
Ghasemzadeh, M. B., Nelson, L. C., Lu, X. Y., and Kalivas, P. W. (1999) Neuro-adaptations in ionotropic and metabotropic glutamate receptor mRNA produced by cocaine treatment. J. Neurochem. 72, 157ā165.
Loftis, J. M. and Janowsky, A. (2000) Regulation of NMDA receptor subunits and nitric oxide synthase expression during cocaine withdrawal. J. Neurochem. 75, 2040ā2050.
Lu, W., Monteggia, L. M., and Wolf, M. E. (1999) Withdrawal from repeated amphetamine administration reduces NMDAR1 expression in the substantia nigra, nucleus accumbens and medial prefrontal cortex. Eur. J. Neurosci. 11, 3167ā3177.
Schenk, S. and Partridge, B. (1997) Effects of acute and repeated administration of N-methyl-d-aspartate (NMDA) into the ventral tegmental area: locomotor activating effects of NMDA and cocaine. Brain Res. 769, 225ā232.
Licata, S. C., Freeman, A. Y., Pierce-Bancroft, A. F., and Pierce, R. C. (2000) Repeated stimulation of L-type calcium channels in the rat ventral tegmental area mimics the initiation of behavioral sensitization to cocaine. Psychopharmacology 152, 110ā118.
Sheng, M. and Lee, S. H. (2001) AMPA receptor trafficking and the control of synaptic transmission. Cell 105, 825ā828.
Ungless, M. A., Whistler, J. L., Malenka, R. C., and Bonci, A. (2001) Single cocaine exposure in vivo induces long-term potentiation in dopamine neurons. Nature 411, 583ā587.
Jones, S., Kornblum, J. L., and Kauer, J. A. (2000) Amphetamine blocks long-term synaptic depression in the ventral tegmental area. J. Neurosci. 20, 5575ā5580.
Thomas, M. J., Malenka, R. C., and Bonci, A. (2000) Modulation of long-term depression by dopamine in the mesolimbic system. J. Neurosci. 20, 5581ā5586.
Kalivas, P. W. and Duffy, P. (1995) D1 receptors modulate glutamate transmission in the ventral tegmental area. J. Neurosci. 15, 5379ā5388.
Xue, C.-J., Ng, J. P., Li, Y., and Wolf, M. E. (1996) Acute and repeated systemic amphetamine administration: effects on extracellular glutamate, aspartate and serine levels in rat ventral tegmental area and nucleus accumbens. J. Neurochem. 67, 352ā363.
Fiorillo, C. D. and Williams, J. T. (2000) Selective inhibition by adenosine of mGluR IPSPs in dopamine neurons after cocaine treatment. J. Neurophysiol. 83, 1307ā1314.
Paladini, C. A., Fiorillo, C. D., Morikawa, H., and Williams, J. T. (2001) Amphetamine selectively blocks inhibitory glutamate transmission in dopamine neurons. Nat. Neurosci. 4, 275ā281.
Wolf, M. E. (2002) Addiction: making the connection between behavioral changes and neuronal plasticity in specific circuits. Mol. Intervent. 2, 146ā157.
Chiamulera, C., Epping-Jordan, J. P., Zocchi, A., et al. (2001) Reinforcing and locomotor stimulant effects of cocaine are absent in mGluR5 null mutant mice. Nat. Neurosci. 4, 873ā874.
Mao, L., Conquet, F., and Wang, J. Q. (2001) Augmented motor activity and reduced striatal preprodynorphin mRNA induction in response to acute amphetamine administration in metabotropic glutamate receptor 1 knockout mice. Neuroscience 106, 303ā312.
Vekovischeva, O. Y., Zamanillo, D., Echenko, O., et al. (2001) Morphine-induced dependence and sensitization are altered in mice deficient in AMPA-type glutamate receptor-A subunits. J. Neurosci. 21, 4451ā4459.
White, F. J. and Kalivas, P. W. (1998) Neuroadaptations involved in amphetamine and cocaine addiction. Drug Alcohol. Depend. 51, 141ā153.
Nicola, S. M., Surmeier, D. J., and Malenka, R. C. (2000) Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens. Annu. Rev. Neurosci. 232, 185ā215.
Lu, W., Chen, H., Xue, C.-J., and Wolf, M. E. (1997) Repeated amphetamine administration alters the expression of mRNA for AMPA receptor subunits in rat nucleus accumbens and prefrontal cortex. Synapse 26, 269ā280.
Lu, W. and Wolf, M. E. (1999) Repeated amphetamine administration alters AMPA receptor subunit expression in rat nucleus accumbens and medial prefrontal cortex. Synapse 32, 119ā131.
Zhang, X-.F., Hu, X.-T., and White, F. J. (1998) Whole-cell plasticity in cocaine withdrawal: reduced sodium currents in nucleus accumbens neurons. J. Neurosci. 18, 488ā498.
Scheggi, S., Mangiavacchi, S., Masi, F., Gambarana, C., Tagliamonte, A., and De Montis, M. G. (2002) Dizocilpine infusion has a different effect in the development of morphine and cocaine sensitization: behavioral and neurochemical aspects. Neuroscience 109, 267ā274.
Kelz, M. B., Chen, J., Carlezon, W. A., Jr., et al. (1999) Expression of the transcription factor deltaFosB controls sensitivity to cocaine. Nature 16, 272ā276.
Narita, M., Aoki, T., and Suzuki, T. (2000) Molecular evidence for the involvement of NR2B subunit containing N-methyl-d-aspartate receptors in the development of morphine-induced place preference. Neuroscience 101, 601ā606.
Narita, M., Soma, M., Narita, M., Mizoguchi, H., Tseng, L. F., and Suzuki, T. (2000) Implications of the NR2B subunit-containing NMDA receptor localized in mouse limbic forebrain in ethanol dependence. Eur. J. Pharmacol. 401, 191ā195.
Keys, A. S. and Ellison, G. D. (1999) Long-term alterations in benzodiazepine, muscarinic and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor density following continuous cocaine administration. Pharmacol. Toxicol. 85, 144ā150.
Itzhak, Y. and Martin, J. L. (2000) Cocaine-induced kindling is associated with elevated NMDA receptor binding in discrete mouse brain regions. Neuropharmacology 39, 32ā39.
Szumlinksi, K. K., Herrick-Davis, K., Teitler, M., Maisonneuve, I. M., and Glick, S. D. (2000) Behavioural sensitization to cocaine is dissociated from changes in striatal NMDA receptor levels. NeuroReport 11, 2785ā2788.
Bhargava, H. N. and Kumar, S. (1999) Sensitization to the locomotor stimulant effect of cocaine modifies the binding of [3H]MK-801 to brain regions and spinal cord of the mouse. Gen. Pharmacol. 32, 359ā363.
Mao, L. and Wang, J. Q. (2001) Differentially altered mGluR1 and mGluR5 mRNA expression in rat caudate nucleus and nucleus accumbens in the development and expression of behavioral sensitization to repeated amphetamine administration. Synapse 41, 230ā240.
Swanson, C. J., Baker, D. A., Carson, D., Worley, P. F., and Kalivas, P. W. (2001) Repeated cocaine administration attenuates group I metabotropic glutamate receptor-mediated glutamate release and behavioral activation: a potential role for Homer. J. Neurosci. 21, 9043ā9052.
Bell, K. and Kalivas, P. W. (1996) Context-specific cross sensitization between systemic cocaine and intra-accumbens AMPA infusion in rats. Psychopharmacology 127, 377ā383.
Pierce, R. C., Bell, K., Duffy, P., and Kalivas, P. W. (1996) Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J. Neurosci. 16, 1550ā1560.
Vezina, P. and Kim, J.-H. (1999) Metabotropic glutamate receptors and the generation of locomotor activity: interactions with midbrain dopamine. Neurosci. Biobehav. Rev. 23, 577ā589.
Bibb, J. A., Chen, J., Taylor, J. R., et al. (2001) Effects of chronic exposure to cocaine are regulated by the neuronal protein Cdk5. Nature 410, 376ā380.
Thomas, M. J., Beurrier, C., Bonci, A., and Malenka, R. C. (2001) Long-term depression in the nucleus accumbens: a neural correlate of behavioral sensitization to cocaine. Nat. Neurosci. 4, 1217ā1223.
Wolf, M. E., Dahlin, S. L., Xu, H.-T., Xue, C.-J., and White, K. (1995) Effects of lesions of prefrontal cortex, amygdala, or fornix on behavioral sensitization to amphetamine: comparison with N-methyl-d-aspartate antagonists. Neuroscience 69, 417ā439.
Cador, M., Bjijou, Y., Cailhol, S., and Stinus, L. (1999) d-Amphetamine-induced behavioral sensitization: implication of a glutamatergic medial prefrontal cortex-ventral tegmental area innervation. Neuroscience 94, 705ā721.
Li, Y., Hu, X.-T., Berney, T. G., et al. (1999) Both glutamate receptor antagonists and prefrontal cortex lesions prevent induction of cocaine sensitization and associated neuroadaptations. Synapse 34, 169ā180.
Pierce, R. C., Reeder, D. C., Hicks, J., Morgan, Z. R., and Kalivas, P. W. (1998) Ibotenic acid lesions of the dorsal prefrontal cortex disrupt the expression of behavioral sensitization to cocaine. Neuroscience 82, 1103ā1114.
Li, Y. and Wolf, M. E. (1997) Ibotenic acid lesions of prefrontal cortex do not prevent expression of behavioral sensitization to amphetamine. Behav. Brain Res. 84, 285ā289.
Li, Y., Wolf, M. E., and White, F. J. (1999) The expression of cocaine sensitization is not prevented by MK-801 or ibotenic acid lesions of the medial prefrontal cortex. Behav. Brain Res. 104, 119ā125.
Karler, R., Calder, L. D., Thai, D. K., and Bedingfield, J. B. (1998) The role of dopamine in the mouse frontal cortex: a new hypothesis of behavioral sensitization to amphetamine and cocaine. Pharmacol. Biochem. Behav. 61, 435ā443.
Prasad, B. M., Hochstatter, T., and Sorg, B. A. (1999) Expression of cocaine sensitization: regulation by the medial prefrontal cortex. Neuroscience 88, 765ā774.
Peterson, J. D., Wolf, M. E., and White, F. J. (2000) Altered responsiveness of medial prefrontal cortex neurons to glutamate and dopamine after withdrawal from repeated amphetamine treatment. Synapse 36, 342ā344.
Chefer, V. I., Moron, J. A., Hope, B., Rea, W., and Shippenberg, T. S. (2000) Kappa-opioid receptor activation prevents alterations in mesocortical dopamine neurotransmission that occur during abstinence from cocaine. Neuroscience 101, 619ā627.
Hedou, G., Homberg, J., Feldon, J., and Heidbreder, C. A. (2001) Expression of sensitization to amphetamine and dynamics of dopamine neurotransmission in different laminae of the rat medial prefrontal cortex. Neuropharmacology 40, 366ā382.
Stephans, S. E. and Yamamoto, B. K. (1995) Effect of repeated methamphetamine administrations on dopamine and glutamate efflux in rat prefrontal cortex. Brain Res. 700, 991ā906.
Reid, M. S., Hsu, K., Jr., and Berger, S. P. (1997) Cocaine and amphetamine preferentially stimulate glutamate release in the limbic system: studies on the involvement of dopamine. Synapse 27, 95ā105.
Del Arco, A., Martinez, R., and Mora, F. (1998) Amphetamine increases extracellular concentrations of glutamate in the prefrontal cortex of the awake rat: a microdialysis study. Neurochem. Res. 23, 1153ā1158.
Hotsenpiller, G. and Wolf, M. E. Extracellular glutamate levels in prefrontal cortex during the expression of associative responses to cocaine related stimuli. Neuropharmacology, in press.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
Ā© 2003 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Wolf, M.E. (2003). Effects of Psychomotor Stimulants on Glutamate Receptor Expression. In: Wang, J.Q. (eds) Drugs of Abuse. Methods In Molecular Medicineā¢, vol 79. Humana Press. https://doi.org/10.1385/1-59259-358-5:13
Download citation
DOI: https://doi.org/10.1385/1-59259-358-5:13
Publisher Name: Humana Press
Print ISBN: 978-1-58829-057-1
Online ISBN: 978-1-59259-358-3
eBook Packages: Springer Protocols