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The Journal of Neuroscience, October 1, 2001, 21(19):7831-7840
Incentive Sensitization by Previous Amphetamine Exposure:
Increased Cue-Triggered "Wanting" for Sucrose Reward
Cindy L.
Wyvell and
Kent C.
Berridge
Department of Psychology, University of Michigan, Ann Arbor,
Michigan 48109
We reported previously that an amphetamine microinjection into the
nucleus accumbens enables Pavlovian reward cues in a conditioned incentive paradigm to trigger excessive instrumental pursuit. Here we
show that sensitization caused by previous amphetamine administration
also causes reward cues to trigger excessive pursuit of their
associated reward, even when sensitized rats are tested in a drug-free
state. Rats learned to lever press for sucrose pellets, and they
separately learned to associate sucrose pellets with Pavlovian cues (30 sec auditory cues). Amphetamine sensitization was induced by six daily
injections of amphetamine (3 mg/kg, i.p.; controls received saline).
Rats were tested for lever pressing under extinction conditions 10 d later, after a bilateral microinjection of intra-accumbens vehicle or
amphetamine (5 µg/0.5 µl per side). Cue-triggered pursuit of
sucrose reward was assessed by increases in pressing on the
sucrose-associated lever during intermittent presentations of a free
conditioned stimulus (CS+) sucrose cue. Sensitized rats pressed
at normal levels during baseline and during the CS , but the CS+
triggered 100% greater increases in pressing from sensitized rats than
from control rats after vehicle microinjection. Sensitization therefore
enhanced the incentive salience attributed to the CS+ even when rats
were tested while drug-free. For control rats, a microinjection of
intra-accumbens amphetamine was needed to produce the same enhancement
of cue-triggered reward "wanting." The amphetamine microinjection
also interacted synergistically in sensitized rats to produce intrusive
cue-triggered pursuit behaviors (e.g., investigatory
sniffing) that interfered with goal-directed lever pressing. These
results support the incentive-sensitization theory postulate that
sensitization causes excessive cue-triggered "wanting" for
an associated reward.
Key words:
amphetamine; nucleus accumbens; mesolimbic; incentive sensitization; addiction; cue; Pavlovian; instrumental; dopamine; incentive salience; reward; conditioned reinforcement
Copyright © 2001 Society for Neuroscience 0270-6474/01/21197831-10$05.00/0
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