Real-Time Measurements of Phasic Changes in Extracellular Dopamine Concentration in Freely Moving Rats by Fast-Scan Cyclic Voltammetry - Drugs of Abuse: Neurological Reviews and Protocols - page 449

of Rebec et al. (1) are consistent with a role for phasic dopamine in alerting
and attention processes.
5.3. Cocaine Self-Administration
Extracellular dopamine has previously been measured during cocaine self-
administration with both electrochemical (27) and microdialysis techniques
(28) . The preliminary data presented here were obtained by monitoring
extracellular dopamine using fast-scan cyclic voltammetry with much better
temporal resolution (25-12,000+ times greater) than previous studies.
Rats ( n = 3) were surgically implanted with indwelling jugular catheters.
Following 1 wk of recovery, they were trained to self-administer cocaine over a
2-h behavioral session. Each active lever-press response (fi xed-ratio 1 schedule
with 20 s time out) resulted in a 0.33 mg of intravenous infusion of cocaine (6 s)
paired with a tone/houselight stimulus (20 s). Once stable self-administration
behavior was seen for at least 3 consecutive days, voltammetry surgery was
performed. Following recovery, rats were allowed to self-administer cocaine
until stable behavior was reestablished (1-2 d). On the experimental day, a
carbon fi ber microelectrode was lowered into the core of the nucleus accumbens
and dopamine was monitored throughout the session. Electrically stimulated
(24 pulses, 60 Hz) release of dopamine was monitored before and after rats
were allowed to self-administer cocaine to verify that the working electrode was
in a dopamine-rich area. At the beginning of the cocaine self-administration
session rats typically lever-pressed two to four times in quick succession
(termed load-up behavior) and then approx every 5 min for the remainder
of the session.
Transient (~5 s) increases in dopamine concentration (75-150 n M ) were seen
immediately following lever-presses for cocaine ( Fig. 4 ). These were concur-
rent with the onset of the tone and houselight (paired with cocaine delivery).
Because the observed dopamine transients ended within 1-5 s of the onset of
cocaine delivery, they are probably not related solely to a direct pharmacologi-
cal effect of cocaine. Indeed, preliminary fi ndings indicate that they are still
present for a lever-press when the cocaine pump is switched off. Instead, these
transient changes in dopamine are likely related to the goal-directed behaviors
for intravenous cocaine, as well as associative factors operating within the
self-administration context.
5.4. Conclusions
These data establish that fast-scan cyclic voltammetry can measure rapid,
transient dopaminergic events in behaving rats on a physiological time scale,
and invite research on phasic dopaminergic transmission during a variety of
experimental paradigms, including motivation and learning. The time resolution