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.

Increased dopamine release in the human amygdala during performance of cognitive tasks


Accumulating data support a critical involvement of dopamine in the modulation of neuronal activity related to cognitive processing. The amygdala is a major target of midbrain dopaminergic neurons and is implicated in learning and memory processes, particularly those involving associations between novel stimuli and reward. We used intracerebral microdialysis to directly sample extracellular dopamine in the human amygdala during the performance of cognitive tasks. The initial transition from rest to either a working memory or a reading task was accompanied by significant increases in extracellular dopamine concentration of similar magnitude. During a sustained word paired-associates learning protocol, increase in dopamine release in the amygdala related to learning performance. These data provide evidence for sustained activation of the human mesolimbic dopaminergic system during performance of cognitive tasks.

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

Access options

Rent or buy this article

Prices vary by article type



Prices may be subject to local taxes which are calculated during checkout

Figure 1: Coronal MRI section depicting electrodes placed horizontally in the left and right amygdala (left side of the brain is on the right and vice versa).
Figure 2: Changes in extracellular dopamine in the amygdala during the two sequences: reading–memory–reading and memory–reading–memory.
Figure 3: Dialysate dopamine concentrations from individual probes placed in the amygdala of subjects performing the memory–reading–memory sequence.
Figure 4: Dialysate dopamine concentrations from individual probes placed in the amygdala of subjects performing the reading–memory–reading sequence.
Figure 5: Increase in amygdala dialysate dopamine concentration during execution of a paired associates task.

Similar content being viewed by others


  1. Goldman-Rakic, P. S. The cortical dopamine system: role in memory and cognition. Adv. Pharmacol. 42, 707–711 (1998).

    Article  CAS  Google Scholar 

  2. Williams, G. V. & Goldman-Rakic, P. S. Modulation of memory fields by dopamine D1 receptors in prefrontal cortex. Nature 376, 572–575 (1995).

    Article  CAS  Google Scholar 

  3. Everitt, B. J. et al. Associative processes in addiction and reward. The role of amygdala-ventral striatal subsystems. Ann. NY Acad. Sci. 877, 412–438 (1999).

    Article  CAS  Google Scholar 

  4. Koob, G. F. The role of the striatopallidal and extended amygdala systems in drug addiction. Ann. NY Acad. Sci. 877, 445–460 (1999).

    Article  CAS  Google Scholar 

  5. Maren, S. & Fanselow, M. S. The amygdala and fear conditioning: has the nut been cracked? Neuron 16, 237–240 (1996).

    Article  CAS  Google Scholar 

  6. Rosenkranz, J. A. & Grace, A. A. Modulation of basolateral amygdala neuronal firing and afferent drive by dopamine receptor activation in vivo. J. Neurosci. 19, 11027–11039 (1999).

    Article  CAS  Google Scholar 

  7. Nader, K. & LeDoux, J. E. Inhibition of the mesoamygdala dopaminergic pathway impairs the retrieval of conditioned fear associations. Behav. Neurosci. 113, 891–901 (1999).

    Article  CAS  Google Scholar 

  8. Schultz, W., Apicella, P. & Ljungberg, T. Responses of monkey dopamine neurons to reward and conditioned stimuli during successive steps of learning a delayed response task. J. Neurosci. 13, 900–913 (1993).

    Article  CAS  Google Scholar 

  9. Ljungberg, T., Apicella, P. & Schultz, W. Responses of monkey midbrain dopamine neurons during delayed alternation performance. Brain. Res. 567, 337–341 (1991).

    Article  CAS  Google Scholar 

  10. Schultz, W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1–27 (1998).

    Article  CAS  Google Scholar 

  11. Thomas, M. J., Malenka, R. C. & Bonci, A. Modulation of long-term depression by dopamine in the mesolimbic system. J. Neurosci. 20, 5581–5586 (2000).

    Article  CAS  Google Scholar 

  12. Garcia, R., Vouimba, R. M., Baudry, M. & Thompson, R. F. The amygdala modulates prefrontal cortex activity relative to conditioned fear. Nature 402, 294–296 (1999).

    Article  CAS  Google Scholar 

  13. Fried, I. et al. Cerebral microdialysis combined with single-neuron and electroencephalographic recording in neurosurgical patients. J. Neurosurg. 91, 697–705 (1999).

    Article  CAS  Google Scholar 

  14. Fallon, J. H., Koziell, D. A. & Moore, R. Y. Catecholamine innervation of the basal forebrain. II. Amygdala, suprarhinal cortex and entorhinal cortex. J. Comp. Neurol. 180, 509–532 (1978).

    Article  CAS  Google Scholar 

  15. Ljungberg, T., Apicella, P. & Schultz, W. Responses of monkey dopamine neurons during learning of behavioral reactions. J. Neurophysiol. 67, 145–163 (1992).

    Article  CAS  Google Scholar 

  16. Di Chiara, G. et al. Drug addiction as a disorder of associative learning. Role of nucleus accumbens shell/extended amygdala dopamine. Ann. NY Acad. Sci. 877, 461–485 (1999).

    Article  CAS  Google Scholar 

  17. Robinson, T. E. & Berridge, K. C. The neural basis of drug craving: an incentive-sensitization theory of addiction. Brain Res. Rev. 18, 247–291 (1993).

    Article  CAS  Google Scholar 

  18. Spanagel, R. & Weiss, F. The dopamine hypothesis of reward: past and current status. Trends Neurosci. 22, 521–527 (1999).

    Article  CAS  Google Scholar 

  19. Chesselet, M. F. Presynaptic regulation of neurotransmitter release in the brain: facts and hypothesis. Neuroscience 12, 347–375 (1984).

    Article  CAS  Google Scholar 

  20. Daniels, G. M. & Amara, S. G. Regulated trafficking of the human dopamine transporter. Clathrin-mediated internalization and lysosomal degradation in response to phorbol esters. J. Biol. Chem. 274, 35794–35801 (1999).

    Article  CAS  Google Scholar 

  21. Watanabe, M., Kodama, T. & Hikosaka, K. Increase of extracellular dopamine in primate prefrontal cortex during a working memory task. J. Neurophysiol. 78, 2795–2798 (1997).

    Article  CAS  Google Scholar 

  22. Hori, K., Tanaka, J. & Nomura, M. Effects of discrimination learning on the rat amygdala dopamine release: a microdialysis study. Brain Res. 621, 296–300 (1993).

    Article  CAS  Google Scholar 

  23. Koepp, M. J. et al. Evidence for striatal dopamine release during a video game. Nature 393, 266–268 (1998).

    Article  CAS  Google Scholar 

  24. Sawaguchi, T. & Goldman-Rakic, P. S. D1 dopamine receptors in prefrontal cortex: involvement in working memory. Science 251, 947–950 (1991).

    Article  CAS  Google Scholar 

  25. Durstewitz, D., Kelc, M. & Gunturkun, O. A neurocomputational theory of the dopaminergic modulation of working memory functions. J. Neurosci. 19, 2807–2822 (1999).

    Article  CAS  Google Scholar 

  26. Pierce, R. C. & Kalivas, P.W. A circuitry model of the expression of behavioral sensitization to amphetamine-like psychostimulants. Brain Res. Rev. 25, 192–216 (1997).

    Article  CAS  Google Scholar 

  27. Kalivas, P. W. & Nakamura, M. Neural systems for behavioral activation and reward. Curr. Opin. Neurobiol. 9, 223–227 (1999).

    Article  CAS  Google Scholar 

  28. Young, A. M. & Rees, K. R. Dopamine release in the amygdaloid complex of the rat, studied by brain microdialysis. Neurosci. Lett. 249, 49–52 (1998).

    Article  CAS  Google Scholar 

Download references


We thank M. James for technical support, A. Tan for graphics production and I. M. Wainwright for editorial assistance. This study was supported by NIH NINDS grants NS33221, NS02808 and NS33310.

Author information

Authors and Affiliations


Corresponding author

Correspondence to Nigel T. Maidment.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Fried, I., Wilson, C., Morrow, J. et al. Increased dopamine release in the human amygdala during performance of cognitive tasks. Nat Neurosci 4, 201–206 (2001).

Download citation

  • Received:

  • Accepted:

  • 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