Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph


Positron emission tomography (PET) neuroimaging and behavioral assays in rodents are widely used in neuroscience. PET gives insights into the molecular processes of neuronal communication, and behavioral methods analyze the actions that are associated with such processes. These methods have not been directly integrated, because PET studies in animals have until now required general anesthesia to immobilize the subject, which precludes behavioral studies. We present a method for imaging awake, behaving rats with PET that allows the simultaneous study of behavior. Key components include the 'rat conscious animal PET' or RatCAP, a miniature portable PET scanner that is mounted on the rat's head, a mobility system that allows considerable freedom of movement, radiotracer administration techniques and methods for quantifying behavior and correlating the two data sets. The simultaneity of the PET and behavioral data provides a multidimensional tool for studying the functions of different brain regions and their molecular constituents.

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1: RatCAP tomograph and validation.
Figure 2: Animal mobility system.
Figure 3: D2 receptor neuroimaging using bolus injections of [11C]raclopride in the behaving and anesthetized rat.
Figure 4: Transient changes in BPND in relation to behavioral activity during the PET scan.
Figure 5: Transient changes in BPND and behavior after D2 receptor blockade.


  1. Schultz, W. Multiple dopamine functions at different time courses. Annu. Rev. Neurosci. 30, 259–288 (2007).

    Article  CAS  Google Scholar 

  2. Clark, J.J. et al. Chronic microsensors for longitudinal, subsecond dopamine detection in behaving animals. Nat. Methods 7, 126–129 (2010).

    Article  CAS  Google Scholar 

  3. Westerink, B.H.C. Brain microdialysis and its application for the study of animal behaviour. Behav. Brain Res. 70, 103–124 (1995).

    Article  CAS  Google Scholar 

  4. Dombeck, D.A., Khabbaz, A.N., Collman, F., Adelman, T.L. & Tank, D.W. Imaging large-scale neural activity with cellular resolution in awake, mobile mice. Neuron 56, 43–57 (2007).

    Article  CAS  Google Scholar 

  5. Momosaki, S. et al. Rat-PET study without anesthesia: anesthetics modify the dopamine D1 receptor binding in rat brain. Synapse 54, 207–213 (2004).

    Article  CAS  Google Scholar 

  6. Patel, V.D., Lee, D.E., Alexoff, D.L., Dewey, S.L. & Schiffer, W.K. Imaging dopamine release with positron emission tomography (PET) and 11C-raclopride in freely moving animals. Neuroimage 41, 1051–1066 (2008).

    Article  Google Scholar 

  7. Hosoi, R. et al. MicroPET detection of enhanced 18F-FDG utilization by PKA inhibitor in awake rat brain. Brain Res. 1039, 199–202 (2005).

    Article  CAS  Google Scholar 

  8. Harada, N., Ohba, H., Fukumoto, D., Kakiuchi, T. & Tsukada, H. Potential of [18F]β-CFT-FE (2β-carbomethoxy-3β-(4-fluorophenyl)-8-(2-[18F]fluoroethyl)nortropane) as a dopamine transporter ligand: a PET study in the conscious monkey brain. Synapse 54, 37–45 (2004).

    Article  CAS  Google Scholar 

  9. Itoh, T. et al. PET measurement of the in vivo affinity of 11C-(R)-rolipram and the density of its target, phosphodiesterase-4, in the brains of conscious and anesthetized rats. J. Nucl. Med. 50, 749–756 (2009).

    Article  CAS  Google Scholar 

  10. Ferris, C.F. et al. Functional magnetic resonance imaging in conscious animals: a new tool in behavioural neuroscience research. J. Neuroendocrinol. 18, 307–318 (2006).

    Article  CAS  Google Scholar 

  11. Kyme, A.Z., Zhou, V.W., Meikle, S.R. & Fulton, R.R. Real-time 3D motion tracking for small animal brain PET. Phys. Med. Biol. 53, 2651–2666 (2008).

    Article  CAS  Google Scholar 

  12. Grace, A.A. The tonic/phasic model of dopamine system regulation: its relevance for understanding how stimulant abuse can alter basal ganglia function. Drug Alcohol Depend. 37, 111–129 (1995).

    Article  CAS  Google Scholar 

  13. Kravitz, A.V. et al. Regulation of parkinsonian motor behaviours by optogenetic control of basal ganglia circuitry. Nature 466, 622–626 (2010).

    Article  CAS  Google Scholar 

  14. White, N.M. Addictive drugs as reinforcers: multiple partial actions on memory systems. Addiction 91, 921–949 (1996).

    Article  CAS  Google Scholar 

  15. Wise, R.A. Dopamine, learning and motivation. Nat. Rev. Neurosci. 5, 483–494 (2004).

    Article  CAS  Google Scholar 

  16. Vaska, P. et al. RatCAP: miniaturized head-mounted PET for conscious rodent brain imaging. IEEE Trans. Nucl. Sci. 51, 2718–2722 (2004).

    Article  Google Scholar 

  17. Pratte, J.-F. The RatCAP front-end ASIC. IEEE Trans. Nucl. Sci. 55, 2727–2735 (2008).

    Article  Google Scholar 

  18. Junnarkar, S.S. et al. Next generation of real time data acquisition, calibration and control system for the RatCAP scanner. IEEE Trans. Nucl. Sci. 55, 220–224 (2008).

    Article  Google Scholar 

  19. Park, S.J. et al. Digital coincidence processing for the RatCAP conscious rat brain PET scanner. IEEE Trans. Nucl. Sci. 55, 510–515 (2008).

    Article  Google Scholar 

  20. Innis, R.B. et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J. Cereb. Blood Flow Metab. 27, 1533–1539 (2007).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  22. Rabiner, E.A. Imaging of striatal dopamine release elicited with NMDA antagonists: is there anything to be seen? J. Psychopharmacol. 21, 253–258 (2007).

    Article  CAS  Google Scholar 

  23. Hassoun, W. et al. PET study of the [11C]raclopride binding in the striatum of the awake cat: effects of anaesthetics and role of cerebral blood flow. Eur. J. Nucl. Med. 30, 141–148 (2003).

    Article  CAS  Google Scholar 

  24. Eilam, D. & Szechtman, H. Biphasic effect of D-2 agonist quinpirole on locomotion and movements. Eur. J. Pharmacol. 161, 151–157 (1989).

    Article  CAS  Google Scholar 

  25. Li, S.-M. Yawning and locomotor behavior induced by dopamine receptor agonists in mice and rats. Behav. Pharmacol. 21, 171–181 (2010).

    Article  CAS  Google Scholar 

  26. Carson, R.E. PET physiological measurements using constant infusion. Nucl. Med. Biol. 27, 657–660 (2000).

    Article  CAS  Google Scholar 

  27. Hillegaart, V. & Ahlenius, S. Effects of raclopride on exploratory locomotor activity, treadmill locomotion, conditioned avoidance behaviour and catalepsy in rats: behavioural profile comparisons between raclopride, haloperidol and preclamol. Pharmacol. Toxicol. 60, 350–354 (1987).

    Article  CAS  Google Scholar 

  28. van den Boss, R., Cools, A.R. & Ogren, S.-O. Differential effects of the selective D2-antagonist raclopride in the nucleus accumbens of the rat on spontaneous and d-amphetamine–induced activity. Psychopharmacology (Berl.) 95, 447–451 (1988).

    Article  CAS  Google Scholar 

  29. Larobina, M., Brunetti, A. & Salvatore, M. Small animal PET: a review of commercially available imaging systems. Curr. Med. Imaging Rev. 2, 187–192 (2006).

    Article  Google Scholar 

  30. Paxinos, G. & Watson, C. The Rat Brain in Stereotaxic Coordinates 6th edn., 243 (Elsevier, London, 2007).

  31. Henn, F.A. & Vollmayr, B. Stress models of depression: Forming genetically vulnerable strains. Neurosci. Biobehav. Rev. 29, 799–804 (2005).

    Article  Google Scholar 

  32. Schulz, D., Mirrione, M.M. & Henn, F.A. Cognitive aspects of congenital learned helplessness and its reversal by the monoamine oxidase (MAO)-B inhibitor deprenyl. Neurobiol. Learn. Mem. 93, 291–301 (2010).

    Article  CAS  Google Scholar 

  33. Ehrin, E. et al. Preparation of 11C-labelled raclopride, a new potent dopamine receptor antagonist: Preliminary PET studies of cerebral dopamine receptors in the monkey. Int. J. Appl. Radiat. Isot. 36, 269–273 (1985).

    Article  CAS  Google Scholar 

  34. Sesack, S.R., Aoki, C. & Pickel, V.M. Ultrastructural localization of D2 receptor-like immunoreactivity in midbrain dopamine neurons and their striatal targets. J. Neurosci. 14, 88–106 (1994).

    Article  CAS  Google Scholar 

Download references


We thank W. Lenz for mechanical design and fabrication; D. Alexoff for assistance with rat handling; S. Park for coincidence-processing methods; W. Schiffer for assistance with data analysis; C. Reiszel for expertise in catheter design; V. Radeka, R. Lecomte and R. Fontaine for contributions to the electronics; J. Logan for advice on kinetic modeling; J. Fowler and the personnel of the Brookhaven National Laboratory PET center and cyclotron for making the radiotracers available for our studies and N. Volkow for proposing the idea of a conscious-animal PET scanner. The research was carried out at Brookhaven National Laboratory under contract number DE-AC02-98CH10886 with the US Department of Energy and funded by the Department of Energy's Office of Biological and Environmental Research.

Author information

Authors and Affiliations



D.S. proposed and carried out most of the rat work, acquired and analyzed behavioral data and wrote the paper. S.S. developed quantitative PET data processing and reconstruction software and acquired and analyzed PET data. S.S.J. developed front-end and data acquisition electronics, software and firmware. J.-F.P. developed the front-end microchip. M.L.P. developed data processing and image reconstruction software. S.P.S. assembled and debugged scanner and mechanics. B.R. and S.H.M. acquired rat data and performed data analysis. S.K. constructed scanner components. F.A.H. contributed to the behavioral neuroimaging experiments. P.O. oversaw and conceived key aspects of the electronics. C.L.W. oversaw development of the scanner, especially the front-end detectors and electronics. D.J.S. oversaw development of the scanner and performed rat studies and data analysis. P.V. oversaw development of the scanner, software and mechanics, performed rat studies and wrote the paper.

Corresponding author

Correspondence to Paul Vaska.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Note (PDF 162 kb)

Supplementary Software

Raw code and input files necessary to process data from the RatCAP scanner into images, including coincidence processing and image reconstruction. (ZIP 199379 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Schulz, D., Southekal, S., Junnarkar, S. et al. Simultaneous assessment of rodent behavior and neurochemistry using a miniature positron emission tomograph. Nat Methods 8, 347–352 (2011).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing