Abstract
In our previous positron emission tomography studies striatal binding for both [11C]SCH23390 and [11C]N-methylspiperone (NMSP) were decreased in the rat brain on the last day of chronic (14 days) binge cocaine administration. We have found that [11C]SCH23390 binding to dopamine D1 receptors returns to saline control levels within ten days withdrawal from chronic binge cocaine and remains at control levels after 21 days withdrawal. An 18% decrease in [11C]NMSP binding to dopamine D2 receptors was observed after ten days withdrawal. However, importantly, after 21 days withdrawal [11C]NMSP binding was at saline control levels. Changes of in vivo [11C]NMSP binding required a longer abstinence period for normalization than [11C]SCH23390 binding. The apparent recovery of dopamine D2 receptors after prolonged abstinence from chronic cocaine and the different rates of normalization for dopamine D1 versus D2 receptors may be critical information for development of pharmacotherapies for cocaine dependent patients.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
References
Branch AD, Unterwald EM, Lee SE, Kreek MJ . (1992): Quantitation of preproenkephalin mRNA levels in brain regions from male Fischer rats following chronic cocaine treatment using a recently developed solution hybridization assay. Mol Brain Res 14: 231–238
Caine SB, Koob GF . (1994): Effects of dopamine D-1 and D-2 antagonists on cocaine self-administration under different schedules of reinforcement in the rat. J Pharmacol Exp Ther 270: 209–218
Clark D, White FJ . (1987): D1 dopamine receptor—the search for a function: A critical evaluation of the D1/D2 dopamine receptor classification and its functional implications. Synapse 1: 347–388
Goeders NE, Kuhar MJ . (1987): Chronic cocaine administration induces opposite changes in dopamine receptors in the striatum and nucleus accumbens. Alcohol Drug Res 7: 207–216
Hammer RP, Egilmez Y, Emmet-Oglesby MW . (1997): Neural mechanisms of tolerance to the effects of cocaine. Behav Brain Res 84: 225–239
Huang SH, Barrio J, Phelps M . (1986): Neuroreceptor assay with positron emission tomography: Equilibrium versus dynamic approach. J Cereb Blood Flow Metab 6: 515–521
Kreuter J, Tsukada H, Schlussman SD, Kakiuchi T, Nishiyama S, Maggos CE, Unterwald EM, Kreek MJ . (1998): Effects of withdrawal from binge pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain as measured by PET. Problems of Drug Dependence 1994. Proceedings of the 59th Annual Scientific Meeting, The College on Problems of Drug Dependence, NIDA Research Monograph (in press).
Kuhar MJ, Pilotte NS . (1996): Neurochemical changes in cocaine withdrawal. Trends Pharmacol Sci 17: 260–264
Kuhar MJ, Ritz MC, Boja JW . (1991): The dopamine hypothesis of the reinforcing properties of cocaine. Trends Neurosci 14: 299–302
Laurier LG, Corrigall WA, George SR . (1994): Dopamine receptor density, sensitivity and mRNA levels are altered following self-administration of cocaine in the rat. Brain Res 634: 31–40
Maisonneuve IM, Ho A, Kreek MJ . (1995): Chronic administration of a cocaine “binge” alters basal extracellular dopamine levels in male rats: An in vivo microdialysis study. J Pharmacol Exp Ther 272: 652–657
Maisonneuve IM, Kreek MJ . (1994): Acute tolerance to the dopamine response induced by a binge pattern of cocaine administration in male rats: An in vivo microdialysis study. J Pharmacol Exp Ther 268: 916–921
Nader M, Mach R, Ehrenkaufer R, Gage H, Morton T . (1998): Longterm downregulation of dopamine D2 receptors following cocaine self-administration in monkeys. Problems of Drug Dependence 1997. Proceedings of the 59th Annual Scientific Meeting, The College on Problems of Drug Dependence, NIDA Research Monograph (in press).
Ritz MC, Lamb RJ, Goldberg SR, Kuhar MJ . (1987): Cocaine receptors on dopamine transporters are related to self-administration of cocaine. Science 237: 1219–1223
Rosetti ZL, Hmaidan Y, Gessa GL . (1992): Marked inhibition of mesolimbic dopamine release: A common feature of ethanol, morphine, cocaine, and amphetamine abstinence in rats. Eur J Pharmacol 221: 227–234
Self DW, Barnhart WJ, Lehman DA, Nestler EJ . (1996): Opposite modulation of cocaine-seeking behavior by d-1- and d-2-like dopamine receptor agonists. Science 271: 1586–1589
Spangler R, Unterwald EM, Kreek MJ . (1993): ‘Binge’ cocaine administration induces a sustained increase of prodynorphin mRNA in rat caudate-putamen. Mol Brain Res 19: 323–327
Tsukada H, Kreuter J, Maggos CE, Unterwald EM, Kakiuchi T, Nishiyama S, Futatsubashi M, Kreek MJ . (1996): Effects of binge pattern cocaine administration on dopamine D1 and D2 receptors in the rat brain: An in vivo study using positron emission tomography. J Neurosci 16: 7670–7677
Unterwald EM, Ho A, Rubenfeld JM, Kreek MJ . (1994): Time course of the development of behavioral sensitization and dopamine receptor up-regulation during binge cocaine administration. J Pharmacol Exp Ther 270: 1387–1396
Volkow ND, Fowler JS, Wolf AP, Schlyer D, Shiue CY, Alpert R, Dewey SL, Logan J, Bendriem B, Christman D, Hitzemann R, Henn F . (1990): Effects of chronic cocaine abuse on postsynaptic dopamine receptors. Am J Psychiatr 147: 719–724
Volkow ND, Fowler JS, Wang GJ, Hitzemann R, Logan J, Schlyer DJ, Dewey SL, Wolf AP . (1993): Decreased dopamine D2 receptor availability is associated with reduced frontal metabolism in cocaine abusers. Synapse 14: 169–177
Wang JQ, McGinty JF . (1997): The full D1 dopamine receptor agonist SKF-82958 induces neuropeptide mRNA in the normosensitive striatum of rats: Regulation of D1/D2 interactions by muscarinic receptors. J Pharmacol Exp Ther 281: 972–982
Watanabe M, Uchida H, Okada H, Shimizu K, Sato N, Yoshikawa E, Ohmura T, Tanaka E . (1992): A high resolution PET for animal studies. IEEE Trans Nucl Sci 11: 577–580
Young LT, Wong DF, Goldman S, Minkin E, Chen C, Matsumura K, Scheffel U, Wagner HN Jr . (1991): Effects of endogenous dopamine on kinetics of [3H]N-methylspiperone and [3H]reclopride binding in the rat brain. Synapse 9: 188–194
Acknowledgements
Supported in part by NIH DA P50–05130 & NIH-DA-K05–00049.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maggos, C., Tsukada, H., Kakiuchi, T. et al. Sustained Withdrawal Allows Normalization of In Vivo [11C]N-Methylspiperone Dopamine D2 Receptor Binding after Chronic Binge Cocaine: A Positron Emission Tomography Study in Rats. Neuropsychopharmacol 19, 146–153 (1998). https://doi.org/10.1016/S0893-133X(98)00009-8
Received:
Revised:
Accepted:
Issue date:
DOI: https://doi.org/10.1016/S0893-133X(98)00009-8
Keywords
This article is cited by
-
Amphetamine Self-Administration Attenuates Dopamine D2 Autoreceptor Function
Neuropsychopharmacology (2014)
-
Influence of cocaine administration patterns on dopamine receptor regulation
Psychopharmacology (2014)
-
Behavioral sensitization to cocaine in rats: evidence for temporal differences in dopamine D3 and D2 receptor sensitivity
Psychopharmacology (2011)
-
The Role of Acetylcholine in Cocaine Addiction
Neuropsychopharmacology (2008)
-
Addiction-Related Alterations in D1 and D2 Dopamine Receptor Behavioral Responses Following Chronic Cocaine Self-Administration
Neuropsychopharmacology (2007)
