Summary
The ability to model aspects of human addictive behaviors in laboratory animals provides an important avenue for gaining insight into the biochemical alterations associated with drug intake and the identification of targets for medication development to treat addictive disorders. The intravenous self-administration procedure provides the means to model the reinforcing effects of abused drugs and to correlate biochemical alterations with drug reinforcement. In this chapter, we provide a detailed methodology for rodent intravenous self-administration and the isolation and preparation of proteins from dissected brain regions for Western blot analysis and high-throughput proteomic analysis. Examples of cocaine-induced alterations in the abundances of ionotropic glutamate receptor subunits in reinforcement-related brain regions are provided.
Key words
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Hemby, S. E. (1999). Recent advances in the biology of addiction. Curr. Psychiatry Rep. 1, 159–165.
Hemby, S. E., Johnson, B. A., and Dworkin, S. I. (1997). Neurobiological basis of drug reinforcement, in Drug Addiction and its Treatment: Nexus of Neuroscience and Behavior (Johnson, B. A., and Roache, J. D. eds., Lippincott-Raven Publishers, Philadelphia, pp. 137–169.
Tannu, N., Mash, D. C., and Hemby, S. E. (2007). Cytosolic proteomic alterations in the nucleus accumbens of cocaine overdose victims. Mol. Psychiatry 12, 55–73.
Tannu, N. S., and Hemby, S. E. (2006). Methods for proteomics in neuroscience. Prog. Brain Res. 158, 41–82.
Tannu, N. S., and Hemby, S. E. (2006) Two-dimensional fluorescence difference gel electrophoresis for comparative proteomics profiling. Nat. Protoc. 1, 1732–1742.
Weeks, J. R. (1962). Experimental morphine addiction: method for automatic intravenous injections in unrestrained rats. Sci. 138, 143–144.
Weeks, J. R. (1972). Long-term intravenous infusions, in Methods in Psychobiology, Vol. 2 (Myers, R. D. ed.), Academic Press, New York, pp. 155–168.
Breiter, H. C., Gollub, R. L., Weisskoff, R. M., Kennedy, D. N., Makris, N., Berke, J.D., Goodman, J.M., Kantor, H.L., Gastfriend, D.R., Riorden, J.P., Mathew, R.T., Rosen, B.R., and Hyman, S.E. (1997). Acute effects of cocaine on human brain activity and emotion. Neuron., 19, 591–611.
Kilts, C. D., Gross, R. E., Ely, T. D., and Drexler, K. P. (2004). The neural correlates of cue-induced craving in cocaine-dependent women. Am. J. Psychiatry 161, 233–241.
Kilts, C. D., Schweitzer, J. B., Quinn, C. K., Gross, R. E., Faber, T. L., Muhammad, F., Ely, T. D., Hoffman, J. M., and Drexler, K. P. (2001) Neural activity related to drug craving in cocaine addiction. Arch. Gen. Psychiatry 58, 334–341.
Hemby, S. E., Co, C., Dworkin, S. I., and Smith, J. E. (1999). Synergistic elevations in nucleus accumbens extracellular dopamine concentrations during self-administration of cocaine/heroin combinations (Speedball) in rats. J. Pharmacol. Exp. Ther. 288, 274–280.
Hemby, S. E., Co, C., Koves, T. R., Smith, J. E. and Dworkin, S. I. (1997). Differences in extracellular dopamine concentrations in the nucleus accumbens during response-dependent and response-independent cocaine administration in the rat. Psychopharmacology (Berl). 133, 7–16.
Pettit, H. O., Ettenberg, A., Bloom, F. E., and Koob, G. F. (1984). Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats. Psychopharmacology 84, 167–173.
Pettit, H. O., Pan, H. T., Parsons, L. H., and Justice, J. B., Jr. (1990). Extracellular concentrations of cocaine and dopamine are enhanced during chronic cocaine administration. J. Neurochem. 55, 798–804.
Zito, K. A., Vickers, G., and Roberts, D. C. (1985). Disruption of cocaine and heroin self-administration following kainic acid lesions of the nucleus accumbens. Pharmacol. Biochem. Behavior 23, 1029–1036.
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, 2397–2403.
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, 274–282.
Tang, W. X., Fasulo, W. H., Mash, D. C., and Hemby, S. E. (2003). Molecular profiling of midbrain dopamine regions in cocaine overdose victims. J. Neurochem. 85, 911–924.
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. Nat. 411, 583–587.
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. Exper. Therapeutics 273, 445–454.
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. Exper. Therapeutics 281, 699–706.
Kalivas, P. W., McFarland, K., Bowers, S., Szumlinski, K., Xi, Z. X., and Baker, D. (2003). Glutamate transmission and addiction to cocaine. Ann. N. Y. Acad. Sci. 1003, 169–175.
Kalivas, P. W., Volkow, N., and Seamans, J. (2005) Unmanageable motivation in addiction: A pathology in prefrontal-accumbens glutamate transmission. Neuron. 45, 647–650.
Borges, K., and Dingledine, R. (200). Molecular pharmacology and physiology of glutamate receptors, in Glutamate and addiction (Herman, B. H., Frankenheim, J., Litten, J. Z., Sheridan, P. H., Weight, F. F., and Zukin, S. R., eds.), Humana, Totawa, NJ, pp. 3–22.
Acknowledgments
The preparation of this chapter was funded in part by DA012498, DA06634, and DA03628 (SEH).
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2009 Humana Press, a part of Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Hemby, S.E., Tannu, N. (2009). Modeling Substance Abuse for Applications in Proteomics. In: Ottens, A., Wang, K. (eds) Neuroproteomics. Methods in Molecular Biology, vol 566. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59745-562-6_5
Download citation
DOI: https://doi.org/10.1007/978-1-59745-562-6_5
Published:
Publisher Name: Humana Press, Totowa, NJ
Print ISBN: 978-1-934115-84-8
Online ISBN: 978-1-59745-562-6
eBook Packages: Springer Protocols