Dopamine fluctuations in the nucleus accumbens during maintenance, extinction, and reinstatement of intravenous D-amphetamine self-administration

Moment-to-moment fluctuations of nucleus accumbens dopamine (DA) were deter mined in rats self-administering or passively receiving "yoked" intravenous infusions of D-amphetamine. The initial lever presses of each session caus ed elevations in DA concentration, usually to an initial peak that was not maintained throughout the rest of the session. As the initial ("loading") i njections were metabolized, DA levels dropped toward baseline but were sust ained at elevated plateaus by subsequent lever pressing that was spaced thr oughout the remainder of the 3 hr sessions. During this period, DA levels f luctuated phasically, time-locked to the cycle of periodic lever pressing. Consistent with the known pharmacological actions and dynamics of amphetami ne, peak DA elevations were seen similar to 10-15 min after each injection, and the mean DA level was at a low point in the phasic cycle at the time o f each new lever press. During extinction periods when saline was substitut ed for amphetamine, DA levels dropped steadily toward baseline levels despi te a dramatic increase in (now-unrewarded) lever pressing. Noncontingent in jections during extinction reinstated lever-pressing behavior and increased nucleus accumbens DA concentrations. These data are consistent with the hy pothesis that under the conditions of this experiment-during periods of amp hetamine intoxication in well-trained animals-the timing of amphetamine sel f-administration comes primarily under the control of extracellular DA conc entrations. 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 a s DA concentrations fall below or increase above that trigger point.