Skip to main content

Free Content Selective serotonin 2A receptor antagonism attenuates the effects of amphetamine on arousal and dopamine overflow in non‐human primates

Download Article:

You have access to the full text article on a website external to Ingenta Connect.

Please click here to view this article on Wiley Online Library.

You may be required to register and activate access on Wiley Online Library before you can obtain the full text. If you have any queries please visit Wiley Online Library



The objective of the present study was to further elucidate the mechanisms involved in the wake‐promoting effects of psychomotor‐stimulants. Many previous studies have tightly linked the effects of stimulants to dopamine neurotransmission, and some studies indicate that serotonin 2A receptors modulate these effects. However, the role of dopamine in arousal is controversial, most notably because dopamine neurons do not change firing rates across arousal states. In the present study, we examined the wake‐promoting effects of the dopamine‐releaser amphetamine using non‐invasive telemetric monitoring. These effects were evaluated in rhesus monkeys as a laboratory animal model with high translational relevance for human disorders of sleep and arousal. To evaluate the role of dopamine in the wake‐promoting effects of amphetamine, we used in vivo microdialysis targeting the caudate nucleus, as this approach provides clearly interpretable measures of presynaptic dopamine release. This is beneficial in the present context because some of the inconsistencies between previous studies examining the role of dopamine in arousal may be related to differences between postsynaptic dopamine receptors. We found that amphetamine significantly and dose‐dependently increased arousal at doses that engendered higher extracellular dopamine levels. Moreover, antagonism of serotonin 2A receptors attenuated the effects of amphetamine on both wakefulness and dopamine overflow. These findings further elucidate the role of dopamine and serotonin 2A receptors in arousal, and they suggest that increased dopamine neurotransmission may be necessary for the wake‐promoting effects of amphetamine, and possibly other stimulants.

Document Type: Research Article


Publication date: 2013-10-01

  • Access Key
  • Free content
  • Partial Free content
  • New content
  • Open access content
  • Partial Open access content
  • Subscribed content
  • Partial Subscribed content
  • Free trial content
Cookie Policy
Cookie Policy
Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out more