Amphetamine microinjection into the nucleus accumbens shell enhanced the ability of a Pavlovian reward cue to trigger increased instrumental performance for sucrose reward in a pure conditioned incentive paradigm. Rats were first trained to press one of two levers to obtain sucrose pellets. They were separately conditioned to associate a Pavlovian cue (30 sec light) with free sucrose pellets. On test days, the rats received bilateral microinjection of intra-accumbens vehicle or amphetamine (0.0, 2.0, 10.0, or 20.0 g/0.5 l), and lever pressing was tested in the absence of any reinforcement contingency, while the Pavlovian cue alone was freely presented at intervals throughout the session. Amphetamine microinjection selectively potentiated the cue-elicited increase in sucrose-associated lever pressing, although instrumental responding was not reinforced by either sucrose or the cue during the test. Intra-accumbens amphetamine can therefore potentiate cue-triggered incentive motivation for reward in the absence of primary or secondary reinforcement. Using the taste reactivity measure of hedonic impact, it was shown that intra-accumbens amphetamine failed to increase positive hedonic reaction patterns elicited by sucrose (i.e., sucrose "liking") at doses that effectively increase sucrose "wanting." We conclude that nucleus accumbens dopamine specifically mediates the ability of reward cues to trigger "wanting" (incentive salience) for their associated rewards, independent of both hedonic impact and response reinforcement.

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 microg/0.5 microl 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.

Although previous studies have shown that pharmacological agents, such as buprenorphine, and alternative nondrug reinforcers, such as money or sweetened solutions, reduce cocaine self-administration, few studies have examined the combined effects of these two approaches. The purpose of the present study was to evaluate the effects of the opioid partial against buprenorphine (0.1 mg/kg) and concurrent access to either water or a glucose plus saccharin solution (G+S, 3% and 0.125% wt/vol) in rats self-administering intravenous (IV) cocaine (0.4 mg/kg per infusion) under fixed-ratio schedules (FR2, 8 or 32). One group had concurrent access to water and another group had concurrent access to G+S. After 3 consecutive days of stable cocaine self-administration, a single buprenorphine injection (0.1 mg/kg IV) was administered 30 min before the start of the experimental session for 3 consecutive days. To summarize the results, (1) the presence of an alternative non-drug reinforcer significantly reduced cocaine self-administration, (2) buprenorphine selectively decreased cocaine, but not water or G+S, self-administration; (3) the decrease in cocaine infusions by buprenorphine was greatest on the first day of buprenorphine administration; and (4) expressed as a percentage of baseline conditions, the combination of buprenorphine and G+S produced a greater decrease in cocaine self-administration than either buprenorphine or G+S alone. These results indicate that combined treatment with buprenorphine and concurrent access to a sweetened solution is a more effective strategy for reducing cocaine self-administration than either strategy alone.

Food deprivation has been shown to increase the self-administration of a wide variety of drugs in a number of different species. However, the effects of food deprivation on other phases of drug taking have not been established. The purpose of the present study was to evaluate the effects of food deprivation on reinstatement of responding for cocaine. Rats trained to self-administer 0.2, 0.4, or 1.0 mg/kg cocaine intravenously (IV) under a fixed-ratio 1 schedule for the first 2 h during daily 7-h sessions were fed either before or after the experimental session. During hours 3-7, rats self-administered saline. Saline replaced cocaine in the infusion pumps at the beginning of hour 3 and a priming injection of either saline or cocaine (0.32, 1.0, or 3.2 mg/kg IV) was administered at the beginning of hour 4. The number of infusions that was self-administered was measured throughout the 7-h session. During hours 1 and 2 when cocaine was available, the number of infusions was inversely related to cocaine dose. During hour 3, rats typically self-administered several infusions of saline, which gradually decreased to near-zero levels by hours 4-7 (extinction responding). A priming injection of cocaine administered at the beginning of hour 4 reinstated responding in a dose-related manner. The magnitude of extinction responding during hour 3 and reinstatement of responding during hour 4 were similar regardless of cocaine maintenance dose.(ABSTRACT TRUNCATED AT 250 WORDS)

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