Differential Regulation of Ionotropic Glutamate Receptor Subunits Following Cocaine Self-administration

Overview

Journal Brain Res

Specialty Neurology

Date 2005 Nov 10

PMID 16277980

Citations 37

Authors

Scott E Hemby

Brian Horman

Wenxue Tang

Affiliations

Soon will be listed here.

Abstract

Previous examination of binge cocaine self-administration and 2 week withdrawal from cocaine self-administration on ionotropic glutamate receptor subunit (iGluRs) protein levels revealed significant alterations in iGluR protein levels that differed between the mesocorticolimbic and nigrostriatal pathways. The present study was undertaken to extend the examination of cocaine-induced alterations in iGluR protein expression by assessing the effects of acute withdrawal (15-16 h) from limited access cocaine self-administration (8 h/day, 15 days). Western blotting was used to compare levels of iGluR protein expression (NR1-3B, GluR1-7, KA2) in the mesolimbic (ventral tegmental area, VTA; nucleus accumbens, NAc; and prefrontal cortex, PFC) and nigrostriatal pathways (substantia nigra, SN and dorsal caudate-putamen, CPu). Within the mesolimbic pathway, reductions were observed in NR1 and GluR5 immunoreactivity in the VTA although no significant alterations were observed in any iGluR subunits in the NAc. In the PFC, NR1 was significantly upregulated while GluR2/3, GluR4, GluR5, GluR6/7, and KA2 were decreased. Within the nigrostriatal pathway, NR1, NR2A, NR2B, GluR1, GluR6/7 and KA2 were increased in the dorsal CPu, whereas no significant changes were observed in the SN. The results demonstrate region- and pathway-specific alterations in iGluR subunit expression following limited cocaine self-administration and suggest the importance for the activation of pathways that are substrates of the reinforcing and motoric effects of cocaine.

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References

Terwilliger R, Sevarino K, Crain S, Nestler E . A general role for adaptations in G-proteins and the cyclic AMP system in mediating the chronic actions of morphine and cocaine on neuronal function. Brain Res. 1991; 548(1-2):100-10. DOI: 10.1016/0006-8993(91)91111-d. View

Hemby S, Co C, Dworkin S, Smith J . Synergistic elevations in nucleus accumbens extracellular dopamine concentrations during self-administration of cocaine/heroin combinations (Speedball) in rats. J Pharmacol Exp Ther. 1998; 288(1):274-80. View

Di Chiara G, Imperato A . Drugs abused by humans preferentially increase synaptic dopamine concentrations in the mesolimbic system of freely moving rats. Proc Natl Acad Sci U S A. 1988; 85(14):5274-8. PMC: 281732. DOI: 10.1073/pnas.85.14.5274. View

Haile C, Hiroi N, Nestler E, Kosten T . Differential behavioral responses to cocaine are associated with dynamics of mesolimbic dopamine proteins in Lewis and Fischer 344 rats. Synapse. 2001; 41(3):179-90. DOI: 10.1002/syn.1073. View

Pierce R, Bell K, Duffy P, Kalivas P . Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization. J Neurosci. 1996; 16(4):1550-60. PMC: 6578548. View

Self D, Genova L, Hope B, Barnhart W, Spencer J, Nestler E . Involvement of cAMP-dependent protein kinase in the nucleus accumbens in cocaine self-administration and relapse of cocaine-seeking behavior. J Neurosci. 1998; 18(5):1848-59. PMC: 6792608. View

Hemby S, Smith J, Dworkin S . The effects of eticlopride and naltrexone on responding maintained by food, cocaine, heroin and cocaine/heroin combinations in rats. J Pharmacol Exp Ther. 1996; 277(3):1247-58. View

Wise R, Bozarth M . A psychomotor stimulant theory of addiction. Psychol Rev. 1987; 94(4):469-92. View

Tang W, Wesley M, Freeman W, Liang B, Hemby S . Alterations in ionotropic glutamate receptor subunits during binge cocaine self-administration and withdrawal in rats. J Neurochem. 2004; 89(4):1021-33. PMC: 3843358. DOI: 10.1111/j.1471-4159.2004.02392.x. View

10.

Lu W, Monteggia L, Wolf M . Repeated administration of amphetamine or cocaine does not alter AMPA receptor subunit expression in the rat midbrain. Neuropsychopharmacology. 2001; 26(1):1-13. DOI: 10.1016/S0893-133X(01)00272-X. View

11.

Hemby S, Tang W, Muly E, Kuhar M, Howell L, Mash D . Cocaine-induced alterations in nucleus accumbens ionotropic glutamate receptor subunits in human and non-human primates. J Neurochem. 2005; 95(6):1785-93. PMC: 3843355. DOI: 10.1111/j.1471-4159.2005.03517.x. View

12.

Ahmed S, Koob G . Long-lasting increase in the set point for cocaine self-administration after escalation in rats. Psychopharmacology (Berl). 1999; 146(3):303-12. DOI: 10.1007/s002130051121. View

13.

Hemby S, Martin T, Co C, Dworkin S, Smith J . The effects of intravenous heroin administration on extracellular nucleus accumbens dopamine concentrations as determined by in vivo microdialysis. J Pharmacol Exp Ther. 1995; 273(2):591-8. View

14.

Nye H, Hope B, Kelz M, Iadarola M, Nestler E . Pharmacological studies of the regulation of chronic FOS-related antigen induction by cocaine in the striatum and nucleus accumbens. J Pharmacol Exp Ther. 1995; 275(3):1671-80. View

15.

Backes E, Hemby S . Discrete cell gene profiling of ventral tegmental dopamine neurons after acute and chronic cocaine self-administration. J Pharmacol Exp Ther. 2003; 307(2):450-9. PMC: 4048547. DOI: 10.1124/jpet.103.054965. View

16.

Carlezon Jr W, Thome J, OLSON V, Brodkin E, Hiroi N, Duman R . Regulation of cocaine reward by CREB. Science. 1998; 282(5397):2272-5. DOI: 10.1126/science.282.5397.2272. View

17.

Koob G, Bloom F . Cellular and molecular mechanisms of drug dependence. Science. 1988; 242(4879):715-23. DOI: 10.1126/science.2903550. View

18.

Donoghue J, Herkenham M . Neostriatal projections from individual cortical fields conform to histochemically distinct striatal compartments in the rat. Brain Res. 1986; 365(2):397-403. DOI: 10.1016/0006-8993(86)91658-6. View

19.

Zahm D, Brog J . On the significance of subterritories in the "accumbens" part of the rat ventral striatum. Neuroscience. 1992; 50(4):751-67. DOI: 10.1016/0306-4522(92)90202-d. View

20.

Berendse H, Voorn P, te Kortschot A, Groenewegen H . Nuclear origin of thalamic afferents of the ventral striatum determines their relation to patch/matrix configurations in enkephalin-immunoreactivity in the rat. J Chem Neuroanat. 1988; 1(1):3-10. View