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The Journal of Neuroscience, May 15, 1999, 19(10):4102-4109
Dopamine Fluctuations in the Nucleus Accumbens during
Maintenance, Extinction, and Reinstatement of Intravenous
D-Amphetamine Self-Administration
Robert
Ranaldi,
Dorothy
Pocock,
Richard
Zereik, and
Roy
A.
Wise
Center for Studies in Behavioral Neurobiology, Concordia
University, Montreal, Québec, Canada H3G 1M5
Moment-to-moment fluctuations of nucleus accumbens dopamine
(DA) were determined in rats self-administering or passively receiving "yoked" intravenous infusions of D-amphetamine.
The initial lever presses of each session caused elevations in DA
concentration, usually to an initial peak that was not maintained
throughout the rest of the session. As the initial ("loading")
injections were metabolized, DA levels dropped toward baseline but were
sustained at elevated plateaus by subsequent lever pressing that was
spaced throughout the remainder of the 3 hr sessions. During this
period, DA levels fluctuated phasically, time-locked to the cycle of
periodic lever pressing. Consistent with the known pharmacological
actions and dynamics of amphetamine, peak DA elevations were seen
~10-15 min after each injection, and the mean DA level was at a low
point in the phasic cycle at the time of each new lever press. During extinction periods when saline was substituted for amphetamine, DA
levels dropped steadily toward baseline levels despite a dramatic increase in (now-unrewarded) lever pressing. Noncontingent injections during extinction reinstated lever-pressing behavior and increased nucleus accumbens DA concentrations. These data are consistent with the
hypothesis that under the conditions of this experiment during periods
of amphetamine intoxication in well-trained animalsthe timing of
amphetamine self-administration comes primarily under the control of
extracellular DA concentrations. The probability of lever pressing
during the maintenance phase is highest when DA concentrations fall
near a characteristic trigger point, a trigger point that is
significantly elevated above baseline, and falls as DA concentrations
fall below or increase above that trigger point.
Key words:
amphetamine; self-administration; microdialysis; reward; rats; extinction; reinstatement
Copyright © 1999 Society for Neuroscience 0270-6474/99/19104102-08$05.00/0
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