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Journal of Neuroscience, Vol 14, 4130-4146, Copyright © 1994 by Society for Neuroscience
Drug- and behavior-associated changes in dopamine-related electrochemical signals during intravenous cocaine self-administration in rats
A Gratton and RA Wise
Douglas Hospital Research Center, Department of Psychiatry, McGill University, Verdun, Quebec, Canada.
High-speed chronoamperometry was used to determine the moment-to-moment and
day-to-day changes in dopamine-related electrochemical signals in the
nucleus accumbens of rats allowed to self-administer cocaine (0.8
mg/kg/injection) intravenously. The first, unexpected, cocaine injection
caused an abrupt and long-lasting decrease in electrochemical signal. The
second and subsequent injections caused shorter decreases in signal that
were followed, beginning 2-3 min after injection, with a return of signal
toward the preinjection baseline. Thus, the signal increased just prior to
each lever press, peaked at the moment of lever pressing, and decreased for
some minutes after each response. Over the first testing session, the
phasic fluctuations kept the signal somewhat below the preinjection
baseline. On the second and subsequent days, there were large increases in
signal following presentation of the light stimulus that marked the onset
of drug availability and that was paired with each cocaine injection; this
light stimulus had no effect on the first day, prior to drug-light
pairings. The first injection of the second and subsequent days caused an
additional increase in signal; the magnitude of the increase was comparable
to that caused by the initial stimulus, and the two increases summated to
elevate voltammetric signals well above the normal baseline. Subsequent
injections caused immediate but short-lived decreases in signal, as were
seen on the first day; again, the signal returned to or rose slightly above
the preinjection level by the time of the next lever press and injection.
No decrease was seen after lever presses when earned injections were
occasionally withheld; rather, the signal continued to increase slowly
until another lever press was made and a subsequent injection was received.
When access to the lever was blocked and the infusion pump was inactivated
at the end of self-administration sessions, the animals became agitated and
the electrochemical signal increased and remained elevated for 20-40 min
before gradually declining toward the original baseline. Thus, the effects
of cocaine on DA-associated signals in nucleus accumbens (1) changed
dramatically during the development of the self-administration habit and
(2) depended on environmental and behavioral as well as pharmacological
factors. In trained animals, cocaine self-administration was accompanied by
a tonic elevation of DA-associated signals and by phasic fluctuations
time-locked to each cocaine injection.
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