Skip to main content

Advertisement

SpringerLink
Log in

Persisting changes in brain glucose uptake following neurotoxic doses of phencyclidine which mirror the acute effects of the drug

  • Rapid Communication
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Phencyclidine (PCP) can induce a model psychosis which has a number of similarities to dementias and schizophrenia. In some cases the psychosis persists for prolonged periods after drug discontinuation.N-Methyl-d-aspartate (NMDA) antagonists such as PCP induce increases in glucose metabolism in a variety of brain structures but most notably in limbic regions such as retrosplenial, piriform, and entorhinal cortex, hippocampus, and olfactory tubercle. When given continuously for several days, these NMDA antagonists induced neural degeneration in these same critical limbic areas. In the present study regional 2-fluorodeoxyglucose (FDG) uptake was measured in rats at both 24 h and 10 days after neurotoxic, 5-day “binge” PCP administration. At 24 h after minipump removal there were persisting and large increases in glucose uptake in many brain regions, with maximal changes in the same limbic structures in which neurotoxicity has been observed. Surprisingly, many of these regions still showed elevated glucose metabolism after 10 days of recovery. These findings suggest an anatomical and neurochemical substrate for the persisting psychosis which can occur following PCP.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  • Allen R, Young S (1978) Phencyclidine induced psychosis. Am J Psychiatry 135:1081–1084

    Google Scholar 

  • Aniline O, Pitts F (1982) Phencyclidine (PCP): a review and perspectives. CRC Crit Rev Toxicol 10:145–177

    Google Scholar 

  • Caldecott-Hazard S, Mazziotta J, Phelps M (1988) Cerebral correlates of depressed behavior in rats, visualized using14C-2-deoxyglucose autoradiography. J Neurosci 8:1951–1961

    Google Scholar 

  • Eison M, Eison A, Ellison G (1981) The regional distribution ofd-amphetamine and local glucose utilization in rat brain during continous amphetamine administration. Exp Brain Res 43:281–288

    Google Scholar 

  • Ellison G (1994) Competitive and non-competitive NMDA antagonists induce similar limbic degeneration. Neuro Report 5:2688–2692

    Google Scholar 

  • Ellison G (1995) TheN-methyl-d-aspartate antagonists phencyclidine, ketamine and dizocilpine as both behavioral and anatomical models of the dementias. Brain Res Rev 20:250–267

    Google Scholar 

  • Ellison G, Switzer R III (1993) Dissimilar patterns of degeneration in brain following four different addictive stimulants. Neuro Report 5:17–20

    Google Scholar 

  • Keys A (1995) Enduring structural and dynamic alterations in the central nervous system following continuous cocaine exposure. Ph D thesis, University of California

  • Fix A, Wightman K, O'Callaghan J (1995) Reactive gliosis induced by MK-801 in the rat posterior cingulate/retrosplenial cortex: GFAP evaluation by sandwich ELISA and immunocytochemistry. Neurotoxicology 16:229–238

    Google Scholar 

  • Gao X, Shirakawa F, Tamminga C (1993) Delayed regional metabolic actions of phencyclidine. Eur J Pharmacol 241:7–15

    Google Scholar 

  • James S, Schnoll S (1976) Phencyclidine: tissue distribution in the rat. Clin Toxicol 9:573–582

    Google Scholar 

  • Javitt D, Zukin S (1991) Recent advantages in the phencyclidine model of schizophrenia. Am J Psychiatr 148:1301–1308

    Google Scholar 

  • Krystal J, Karper L, Seibyl J, Freeman G, Delancy D, Bremner J, Heninger G, Bowers M Jr, Charney D (1994) Subanesthetic effects of the noncompetitive NMDA antagonist, ketamine, in humans. Arch Gen Psychiatry 51:199–214

    Google Scholar 

  • Kurumaji A, McCulloch J (1989) Effects of MK-801 upon local cerebral glucose utilisation in conscious rats and in rats anaesthetised with halothane. J Cereb Bloot Flow Metab 9:786–794

    Google Scholar 

  • Kurumaji A, McCulloch M (1990) Effects of MK-801 upon local cerebral glucose utilisation in conscious rats following unilateral lesion of caudal entorhinal cortex. Brain Res 531:72–82

    Google Scholar 

  • Meltzer H, Holtzman P, Hassan S, Guschwan A (1972) Effects of phencyclidine and stress on plasma CPK and aldolase activity in many. Psychopharmacology 26:44–53

    Google Scholar 

  • Nabeshima T, Sivam S, Tai C, Ho I (1982) Development of dispositional tolerance to phencylidine by osmotic minipump in the mouse. J Pharm Method 7:239–253

    Google Scholar 

  • Nehls D, Kurumaji A, Park C, McCulloch J (1988) Differential effects of competitive and non-competitiveN-methyl-d-aspartate antagonists on glucose use in the limbic system. Neurosci Lett 91:204–210

    Google Scholar 

  • Nehls D, Park C, MacCormack A, McCulloch J (1990) The effects ofN-methyl-d-aspartate receptor blockade with MK-801 upon the relationship between cerebral blood flow and glucose utilization. Brain Res 511:271–279

    Google Scholar 

  • Olney J, Labruyere J, Price M (1989) Pathological changes induced in cerebrocortical neurons by phenclidine and related drugs. Science 244:1360–1362

    Google Scholar 

  • Sharp F, Sagar F, Swanson R (1993) Metabolic mapping with cellular resolution: c-fos vs 2-deoxyglucose. Crit Rev Neurobiol 7:205–228

    Google Scholar 

  • Tamminga C, Tanimoto K, Kul S, Chase T, Contreras P, Rice K, Jackson A, O'Donohue T (1987) PCP-induced alterations in cerebral glucose utilization in rat brain: blockade by metaphit, a PCP-receptor-acylating agent. Synapse 1:497–504

    Google Scholar 

  • Tamminga C, Thaker G, Buchanan R, Kirpatrick B, Alphs L, Chase T, Carpenter W (1992) Limbic system abnormalities identified in schizophrenia using positron emission tomography with fluorodeoxyglucose and neocortical alterations with deficit syndrome. Arch Gen Psychiatry 49:522–530

    Google Scholar 

  • Valentine J, Arnold L, Owens S (1994) Anti-phencyclidine monoclonal Fab fragments markedly alter phencyclidine pharmacokinetics in rats. J Pharmacol Exp Ther 269:1079–1085

    Google Scholar 

  • Waldorf D (1979) A quantitative analysis of 100 PCP users. In: Feldman H, Agar M, Beschner G (eds) Angel dust, an ethnographic study of PCP users. Lexington Books, Lexington, Mass, pp 53–71

    Google Scholar 

  • Weissman A, Marquis K, Moreton J, London E (1989) Effects of self-administered phencyclidine on regional uptake of 2-deoxy-d-1-14C glucose in brain (1989). Neuropharmacology 28:575–583

    Google Scholar 

  • Wessinger W, Owens S (1991) Phencyclidine dependence: the relationship of dose and serum concentrations to operant behavioral effects. J Pharmacol Exp Ther 258:207–215

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Psychology, UCLA, 405 Hilgard Ave, 90024, Los Angeles, CA, USA

    G. D. Ellison & A. S. Keys

Authors
  1. G. D. Ellison
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. S. Keys
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ellison, G.D., Keys, A.S. Persisting changes in brain glucose uptake following neurotoxic doses of phencyclidine which mirror the acute effects of the drug. Psychopharmacology 126, 271–274 (1996). https://doi.org/10.1007/BF02246457

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02246457

Key words

Search

Navigation