Skip to main content

Advertisement

Log in

Initial Comparison of ntPET with Microdialysis Measurements of Methamphetamine-Induced Dopamine Release in Rats: Support for Estimation of Dopamine Curves from PET Data

  • Rapid Communication
  • Published:
Molecular Imaging and Biology Aims and scope Submit manuscript

Abstract

A recently introduced mathematical method for extracting temporal characteristics of neurotransmitter release from dynamic positron emission tomography (PET) data was tested. The method was developed with the hope that by uncovering temporal information about neurotransmitter (nt) dynamics in PET data, researchers could shed new light on mechanisms of psychiatric diseases such as drug abuse and its treatment. In this study, we apply our model-based method, “ntPET”, to 11C-raclopride PET scans of rats in which the dopaminergic response to a microinfusion of methamphetamine in one striatum was assayed simultaneously by microdialysis and PET. Uptake of 11C-raclopride into the untreated contralateral striatum was used as an input to the ntPET model. Direct comparisons of the model-based ntPET analysis and the microdialysis measurements confirmed that ntPET produced dopamine curves that were very similar in timing (takeoff and peak times) to the microdialysis curves. Variances in takeoff and peak times were comparable for the two methods. Neither method detected a false dopamine response to drug in a control animal. The high degree of correspondence between ntPET estimates and microdialysis measurements lends strong support to the idea that temporal information regarding dopamine release exists in dynamic 11C-raclopride PET data and that it can be estimated reliably via ntPET. The method is entirely translatable to human PET imaging.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Constantinescu CC, Bouman C, Morris ED (2007) Nonparametric extraction of transient changes in neurotransmitter concentration from dynamic PET data. IEEE Trans Med Imaging 26:359–373

    Article  PubMed  Google Scholar 

  2. Morris ED, Yoder KK, Wang C, Normandin MD, Zheng QH, Mock B, Muzic RF Jr, Froehlich JC (2005) ntPET: a new application of PET imaging for characterizing the kinetics of endogenous neurotransmitter release. Mol Imaging 4:473–489

    PubMed  Google Scholar 

  3. Normandin MD, Morris ED (2007) Estimating neurotransmitter kinetics with ntPET: a simulation study of temporal precision and effects of biased data. Neuroimage (in press)

  4. Volkow ND, Swanson JM (2003) Variables that affect the clinical use and abuse of methylphenidate in the treatment of ADHD. Am J Psychiatry 160:1909–1918

    Article  PubMed  Google Scholar 

  5. Volkow ND, Ding YS, Fowler JS, Wang GJ, Logan J, Gatley JS, Dewey S, Ashby C, Liebermann J, Hitzemann R et al (1995) Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. Arch Gen Psychiatry 52:456–463

    PubMed  CAS  Google Scholar 

  6. Volkow ND, Fowler JS, Wang GJ, Swanson JM (2004) Dopamine in drug abuse and addiction: results from imaging studies and treatment implications. Mol Psychiatry 9:557–569

    Article  PubMed  CAS  Google Scholar 

  7. Volkow ND, Wang GJ, Fowler JS, Logan J, Franceschi D, Maynard L, Ding YS, Gatley SJ, Gifford A, Zhu W, Swanson JM (2002) Relationship between blockade of dopamine transporters by oral methylphenidate and the increases in extracellular dopamine: therapeutic implications. Synapse 43:181–187

    Article  PubMed  CAS  Google Scholar 

  8. Breier A, Su TP Saunders R, Carson RE, Kolachana BS, de Bartolomeis A, Weinberger DR, Weisenfeld N, Malhotra AK, Eckelman WC, Pickar D (1997) Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proc Natl Acad Sci U S A 94:2569–2574

    Article  PubMed  CAS  Google Scholar 

  9. Laruelle M, Iyer RN, al-Tikriti MS, Zea-Ponce Y, Malison R, Zoghbi SS, Baldwin RM, Kung HF, Charney DS, Hoffer PB, Innis RB, Bradberry CW (1997) Microdialysis and SPECT measurements of amphetamine-induced dopamine release in nonhuman primates. Synapse 25:1–14

    Article  PubMed  CAS  Google Scholar 

  10. Schiffer WK, Alexoff DL, Shea C, Logan J, Dewey SL (2005) Development of a simultaneous PET/microdialysis method to identify the optimal dose of 11C-raclopride for small animal imaging. J Neurosci Methods 144:25–34

    Article  PubMed  CAS  Google Scholar 

  11. Schiffer WK, Volkow ND, Fowler JS, Alexoff DL, Logan J, Dewey SL (2006) Therapeutic doses of amphetamine or methylphenidate differentially increase synaptic and extracellular dopamine. Synapse 59:243–251

    Article  PubMed  CAS  Google Scholar 

  12. Houston GC, Hume SP, Hirani E, Goggi JL, Grasby PM (2004) Temporal characterisation of amphetamine-induced dopamine release assessed with [11C]raclopride in anaesthetised rodents. Synapse 51:206–212

    Article  PubMed  CAS  Google Scholar 

  13. Narendran R, Slifstein M, Hwang DR, Hwang Y, Scher E, Reeder S, Martinez D, Laruelle M (2007) Amphetamine-induced dopamine release: duration of action as assessed with the D2/3 receptor agonist radiotracer (−)-N-[(11)C]propyl-norapomorphine ([11C]NPA) in an anesthetized nonhuman primate. Synapse 61:106–109

    Article  PubMed  CAS  Google Scholar 

  14. Carson RE, Channing MA, Der MG, Herscovitch P, Eckelman WC (2002) In: Senda M, Kimura Y, Herscovitch P (eds) Scatchard analysis with bolus/infusion administration of [11C]raclopride: amphetamine effects in anesthetized monkeys, in brain imaging using PET. Academic, Amsterdam, pp 63–69

  15. Tsukada H, Nishiyama S, Kakiuchi T, Ohba H, Sato K, Harada N (1999) Is synaptic dopamine concentration the exclusive factor which alters the in vivo binding of [11C]raclopride?: PET studies combined with microdialysis in conscious monkeys. Brain Res 841:160–169

    Article  PubMed  CAS  Google Scholar 

  16. Laruelle M (2000) Imaging synaptic neurotransmission with in vivo binding competition techniques: a critical review. J Cereb Blood Flow Metab 20:423–451

    Article  PubMed  CAS  Google Scholar 

  17. Schiffer WK, Gerasimov MR, Bermel RA, Brodie JD, Dewey SL (2000) Stereoselective inhibition of dopaminergic activity by gamma vinyl-GABA following a nicotine or cocaine challenge: a PET/microdialysis study. Life Sci 66:PL169–PL173

    Article  PubMed  CAS  Google Scholar 

  18. Paxinos G, Watson C (1986) The rat brain in stereotaxic coordinates. Academic, San Diego

    Google Scholar 

  19. Schiffer WK, Gerasimov M, Hofmann L, Marsteller D, Ashby CR, Brodie JD, Alexoff DL, Dewey SL (2001) Gamma vinyl-GABA differentially modulates NMDA antagonist-induced increases in mesocortical versus mesolimbic DA transmission. Neuropsychopharmacology 25:704–712

    Article  PubMed  CAS  Google Scholar 

  20. Bungay PM, Morrison PF, Dedrick RL (1990) Steady-state theory for quantitative microdialysis of solutes and water in vivo and in vivo. Life Sci 46:105–119

    Article  PubMed  CAS  Google Scholar 

  21. Farde L, Hall H, Ehrin E, Sedvall G (1986) Quantitative analysis of D2 dopamine receptor binding in the living human brain by PET. Science 231:258–261

    Article  PubMed  CAS  Google Scholar 

  22. Knoess C, Siegel S, Smith A, Newport D, Richerzhagen N, Winkeler A, Jacobs A, Goble RN, Graf R, Wienhard K, Heiss WD (2003) Performance evaluation of the microPET R4 PET scanner for rodents. Eur J Nucl Med Mol Imaging 30:737–747

    Article  PubMed  Google Scholar 

  23. Morris ED, Fisher RE, Alpert NM, Rauch SL, Fischman AJ (1995) In vivo imaging of neuromodulation using positron emission tomography: optimal ligand characteristics and task length for detection of activation. Hum Brain Mapp 3:35–55

    Article  Google Scholar 

  24. Cunningham VJ, Hume, SP, Price GR, Ahier RG, Cremer JE, Jones AK (1991) Compartmental analysis of diprenorphine binding to opiate receptors in the rat in vivo and its comparison with equilibrium data in vitro. J Cereb Blood Flow Metab 11:1–9

    PubMed  CAS  Google Scholar 

  25. Blomqvist G, Pauli S, Farde L, Eriksson L, Persson A, Halldin C (1990) Maps of receptor binding parameters in the human brain—a kinetic analysis of PET measurements. Eur J Nucl Med 16:257–265

    Article  PubMed  CAS  Google Scholar 

  26. Logan J, Fowler JS, Volkow ND, Wang GJ, Ding YS, Alexoff DL (1996) Distribution volume ratios without blood sampling from graphical analysis of PET data. J Cereb Blood Flow Metab 16:834–840

    Article  PubMed  CAS  Google Scholar 

  27. Schweinhardt P, Fransson P, Olson L, Spenger C, Andersson JL (2003) A template for spatial normalisation of MR images of the rat brain. J Neurosci Methods 129:105–113

    Article  PubMed  Google Scholar 

  28. Gonzales RA, Tang A, Robinson DL (2001) Quantitative microdialysis for in vivo studies of pharmacodynamics. In: Liu Y, Lovinger DM (eds) Methods in alcohol-related neuroscience research. CRC, Boca Raton

    Google Scholar 

Download references

Acknowledgments

NIH R21 AA0 15077 to EDM. NIH/NIDA F31-DA15874 to WKS along with support from the U.S. Department of Energy Office of Biological and Environmental Research (USDOE/OBER DE-AC02-98CH10886).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Evan D. Morris.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Morris, E.D., Normandin, M.D. & Schiffer, W.K. Initial Comparison of ntPET with Microdialysis Measurements of Methamphetamine-Induced Dopamine Release in Rats: Support for Estimation of Dopamine Curves from PET Data. Mol Imaging Biol 10, 67–73 (2008). https://doi.org/10.1007/s11307-007-0124-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11307-007-0124-1

Key words

Navigation