Incentive Sensitization by Previous Amphetamine Exposure: Increased Cue-Triggered “Wanting” for Sucrose Reward

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.