Real-time dopamine measurement in awake monkeys

PLoS One. 2014 Jun 12;9(6):e98692. doi: 10.1371/journal.pone.0098692. eCollection 2014.

Abstract

Fast-scan cyclic voltammetry (FSCV) is often used to measure real-time dopamine (DA) concentrations in awake, behaving rodents. Extending this technique to work in monkeys would provide a platform for advanced behavioral studies and a primate model for preclinical research. The present study demonstrates the feasibility of DA recordings in two awake monkeys (Macaca mulatta) using a mixture of techniques adapted from rodent, primate and brain slice work. We developed a long carbon fiber electrode to operate in the larger primate brain. This electrode was lowered into the striatum each day using a recording chamber and a detachable micromanipulator system. A manipulator also moved one or more tungsten stimulating electrodes into either the nearby striatum or the ventral tegmental area/substantia nigra pars compacta (VTA/SNc). We developed an electrical stimulation controller to reduce artifacts during electrical stimulation. We also introduce a stimulation-based methodology for estimating distances between electrodes in the brain. Dopamine responses within the striatum were evoked by either stimulation of the striatum near the FSCV electrode, or stimulation within the VTA/SNc. Unexpected juice rewards also evoked dopamine responses in the ventral striatum. Thus, we demonstrate that robust dopamine responses can be recorded from awake, behaving primates with FSCV. In addition, we describe how a stimulation technique borrowed from the neuroprosthetics field can activate the distributed monkey midbrain dopamine system in a way that mimics rodent VTA stimulation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / physiology*
  • Deep Brain Stimulation / instrumentation
  • Deep Brain Stimulation / methods
  • Dopamine / metabolism*
  • Electroencephalography / instrumentation
  • Electroencephalography / methods*
  • Evoked Potentials
  • Macaca mulatta
  • Male
  • Reward
  • Wakefulness*

Substances

  • Dopamine

Grant support

This work was supported by the Intramural Research Program of the US National Institute of Mental Health (http://www.nimh.nih.gov). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.