Retractable Lever Research Articles

Acute MK-801 increases measures of both sign-tracking and goal-tracking in male Sprague-Dawley rats

Sign-tracking is a Pavlovian conditioned approach behavior thought to be important in understanding cue-driven relapse to drug use, and strategies for reducing sign-tracking may have some benefit in preventing relapse. A previous study successfully employed the NMDA receptor antagonist MK-801 in preventing the development of sign-tracking (but not goal-tracking) in a conditioned approach task. In this study, we focused on whether MK-801 would have similar effects on previously established sign-tracking behavior. MK-801 was administered after training in a standard sign−/goal-tracking task using a retractable lever as a conditioned stimulus and a sucrose pellet as unconditioned stimulus. It was found that MK-801 increased measures of both sign- and goal-tracking in subjects who had previously learned the task. The NMDA receptor appears to play a complex role in governing behavior related to sign-tracking.

Effects of two kinds of noradrenergic ADHD medicines on sign-tracking and goal-tracking in male rats.

Sign- and goal-tracking are behaviors seen in many species when a conditioned stimulus and it's corresponding unconditioned stimulus are presented at separate locations, and have been the focus of studies on appetitive conditioned and drug dependence. The neurochemical basis of sign-tracking is of interest for both studies of basic conditioning and addiction. In this work, I examined the role of norepinephrine by employing two noradrenergic drugs used for attention-deficit hyperactivity disorder (ADHD)-(a) atomoxetine, a norepinephrine reuptake blocker, and (b) guanfacine, an α2A-adrenergic receptor agonist. Sprague-Dawley rats were trained using a standard Pavlovian conditioning procedure with a retractable lever as conditioned stimulus and sucrose pellets as unconditioned stimulus. It was found that while atomoxetine reduced both sign- (both doses) and goal-tracking (only at the higher dose), guanfacine did not have any effect on either behavior. While norepinephrine reuptake blocking may be an effective strategy for reducing sign-tracking, manipulation of the α2A-adrenergic receptor appears less viable. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Memantine decreases measures of sign-tracking and increases measures of goal-tracking in male Sprague Dawley rats

Memantine is a drug which has antagonistic effects at N-methyl-D-aspartate and 5-hydroxytryptamine3 receptors. Its properties may make it especially effective at reducing sign-tracking, a Pavlovian conditioned approach behavior of a conditioned stimulus, which is implicated in relapse to use of addictive drugs, and thereby provide support to patients who attempting to overcome relapse and addiction. Male Sprague-Dawley rats were trained in a Pavlovian conditioning task using a retractable lever as a conditioned stimulus and sucrose pellets as unconditioned stimuli, which can elicit either sign-tracking or goal-tracking (approach of the site of unconditioned stimulus delivery). Subjects in this task are classified in three behavioral phenotypes – sign-tracker, goal-tracker, or intermediate – depending on levels of sign- and goal-tracking shown at the end of training. Afterward drug testing began and the effects of two doses of memantine were compared with vehicle. It was found that memantine acutely reduced measures of sign-tracking and increased goal-tracking measures, depending on behavioral phenotype, with sign-trackers and intermediates showing the strongest effects. The results of this study suggest that memantine may have use in reducing the incentive salience of reward-related cues.

Does vendor breeding colony influence sign- and goal-tracking in Pavlovian conditioned approach? A preregistered empirical replication

Vendor differences are thought to affect Pavlovian conditioning in rats. After observing possible differences in sign-tracking and goal-tracking behaviour with rats from different breeding colonies, we performed an empirical replication of the effect. 40 male Long-Evans rats from Charles River colonies ‘K72’ and ‘R06’ received 11 Pavlovian conditioned approach training sessions (or “autoshaping”), with a lever as the conditioned stimulus (CS) and 10% sucrose as the unconditioned stimulus (US). Each 58-min session consisted of 12 CS-US trials. Paired rats (n = 15/colony) received the US following lever retraction. Unpaired control rats (n = 5/colony) received sucrose during the inter-trial interval. Next, we evaluated the conditioned reinforcing properties of the CS, by determining whether rats would learn to nose-poke into a new, active (vs. inactive) port to receive CS presentations alone (no sucrose). Preregistered confirmatory analyses showed that during autoshaping sessions, Paired rats made significantly more CS-triggered entries into the sucrose port (i.e., goal-tracking) and lever activations (sign-tracking) than Unpaired rats did, demonstrating acquisition of the CS-US association. Confirmatory analyses showed no effects of breeding colony on autoshaping. During conditioned reinforcement testing, analysis of data from Paired rats alone showed significantly more active vs. inactive nosepokes, suggesting that in these rats, the lever CS acquired incentive motivational properties. Analysing Paired rats alone also showed that K72 rats had higher Pavlovian Conditioned Approach scores than R06 rats did. Thus, breeding colony can affect outcome in Pavlovian conditioned approach studies, and animal breeding source should be considered as a covariate in such work.

NLX-101, a cortical 5-HT1A receptor biased agonist, reverses scopolamine-induced deficit in the delayed non-matching to position model of cognition

NLX-101 is a selective, high efficacy, biased agonist at post-synaptic cortical 5-HT1A receptors. We have previously shown that it opposes deficits produced by blockade of NMDA receptors and has pro-cognitive activity of its own. Based on the strong interaction between 5-HT1A receptors and the central cholinergic system, we tested NLX-101 on scopolamine-induced impairment of cognition in a delayed non-matching to position (DNMTP) model. The cholinesterase inhibitor, tacrine, was used as a comparator.In operant chambers with two retractable levers, male rats were trained to press one randomly presented lever during a “sample” phase. Following a time delay of either 1, 5 or 10 s, both levers were then presented, the rat being required to press the correct lever (i.e. the one not previously presented) to receive a food pellet reward.Scopolamine (0.16 mg/kg i.p.) significantly impaired accuracy (i.e. choice of correct lever) at 5 and 10 s delays. In contrast, NLX-101 (0.04, 0.16, 0.63 mg/kg i.p.) did not worsen accuracy, except at 0.63 mg/kg. Moreover, NLX-101 (0.04 and 0.16 mg/kg) dose-dependently and significantly opposed scopolamine-induced impairment for 5 and 10 s delays, with near-total reversal at 10 s. The acetylcholinesterase inhibitor, tacrine, also opposed scopolamine-induced impairment but was less potent and efficacious, with a single significant effect at 2.5 mg/kg and 5 s delay only.The present data suggest that biased agonism at post-synaptic, cortical 5-HT1A receptors could prove useful in neurological or neuropsychiatric pathologies characterized by cognitive deficits consecutive to a reduced central cholinergic tone.

Shifts in intertrial interval duration in autoshaping with rats: Implications for path dependence

Rats exposed to spaced (S) conditions of training, with intertrial intervals (ITIs) averaging 90 s, acquired autoshaping performance (contact with a retractable lever presented 10 s before the response-independent delivery of 5 food pellets) faster than rats exposed to massed (M) training, with ITIs averaging 15 s. Gradual or abrupt transitions between S and M training were followed by concomitant gradual and abrupt changes in behavior. However, S-to-M and M-to-S transitions supported different levels of adjustment. S-to-M transitions were generally less open to competition between sign and goal tracking than M-to-S transitions. These results suggest that responses that become dominant early in training regulate terminal performance after extensive training. Thus, initial massed training promotes strong goal tracking that interferes with sign tracking even under conditions that would otherwise promote sign tracking. By contrast, initial spaced training tends to promote sign tracking that can interfere with goal tracking even when ITI duration favors goal tracking. These results are discussed in the context of the theoretical issue of path dependence. Their implications for learning theory and their potential applicability to the nature of sign and goal tracking endophenotypes in relation to substance use disorders are briefly discussed.

Neurons of the Ventral Tegmental Area Encode Individual Differences in Motivational "Wanting" for Reward Cues.

It has been argued that the dopaminergic system is involved in the attribution of motivational value to reward predictive cues as well as prediction error. To evaluate, dopamine neurons were recorded from male rats performing a Pavlovian approach task containing cues that have both "predictive" and "incentive" properties. All animals learned the predictive nature of the cue (illuminated lever entry into cage), but some also found the cue to be attractive and were motivated toward it ("sign-trackers," STs). "Goal-trackers" (GTs) predominantly approached the location of reward receptacle. Rats were implanted with tetrodes for neural electrophysiological recordings in the ventral tegmental area. Cells were characterized by spike waveform shape and firing rate. Firing rates and magnitudes of responses in relation to Pavlovian behaviors, cue presentation, and reward delivery were assessed. We identified 103 dopamine and 141 nondopamine neurons. GTs and STs both showed responses to the initial lever presentation (CS1) and lever retraction (CS2). However, higher firing rates were sustained during the lever interaction period only in STs. Further, dopamine cells of STs showed a significantly higher proportion of cells responding to both CS1 and CS2. These are the first results to show that neurons from the VTA encode both predictive and incentive cues, support an important role for dopamine neurons in the attribution of incentive salience to reward-paired cues, and underscore the consequences of potential differences in motivational behavior between individuals.SIGNIFICANCE STATEMENT This project serves to determine whether dopamine neurons encode differences in cued approach behaviors and incentive salience. How neurons of the VTA affect signaling through the NAcc and subsequent dopamine release is still not well known. All cues that precede a reward are predictive in nature. Some, however, also have incentive value, in that they elicit approach toward them. We quantified the attribution of incentive salience through cue approach behavior and cue interaction, and the corresponding magnitude of VTA neural firing. We found dopamine neurons of the VTA encode strength of incentive salience of reward cues. This suggests that dopamine neurons specifically in the VTA encode motivation.

Effects of partial reinforcement on autoshaping in inbred Roman high- and low-avoidance rats

Individuals trained under partial reinforcement (PR) typically show a greater resistance to extinction than individuals exposed to continuous reinforcement (CR). This phenomenon is referred to as the PR extinction effect (PREE) and is interpreted as a consequence of uncertainty-induced frustration counterconditioning. In this study, we assessed the effects of PR and CR in acquisition and extinction in two strains of rats, the inbred Roman high- and low-avoidance (RHA and RLA, respectively) rats. These two strains mainly differ in the expression of anxiety, the RLA rats showing more anxiety-related behaviors (hence, more sensitive to frustration) than the RHA rats. At a neurobiological level, mild stress is known to elevate corticosterone in RLA rats and dopamine in RHA rats. We tested four groups of rats (RHA/CR, RHA/PR, RLA/CR, and RLA/PR) in two successive acquisition-extinction phases to try to consolidate the behavioral effects. Animals received training in a Pavlovian autoshaping procedure with retractable levers as the conditioned stimulus, food pellets as the unconditioned stimulus, and lever presses as the conditioned response. In Phase 1, we observed a PREE in lever pressing in both strains, but this effect was larger and longer lasting in RHA/PR than in RLA/PR rats. In Phase 2, reacquisition was fast and the PREE persisted in both strains, although the two PR groups no longer differed in lever pressing. The results are discussed in terms of frustration theory and of uncertainty-induced sensitization of dopaminergic neurons.

Trial-based Discrimination Procedure for Studying Drug Relapse in Rats.

In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('incubate') over time. Animal models of incubation may help in developing treatments for relapse prevention. However, these models have primarily focused on the role of conditioned stimuli (CSs) signaling drug delivery and not on discriminative stimuli (DSs), which signal drug availability and are also known to play a major role in drug relapse. We recently showed that DS-controlled cocaine seeking in rats also incubates during abstinence and persists up to 300 days. We used a trial-based procedure to train male and female rats to discriminate between two light cues: one light cue (DS+) signaled the availability of cocaine reward and the second light cue (DS-) signaled the absence of reward. Rats learned to press a central retractable lever during trials in which the DS+ cue was presented and to suppress responding when the DS- cue was presented. Here, we provide a detailed protocol for the behavioral procedure used in our study. The trial-based design of this behavior lends itself well to time-locked in vivo recording and manipulation approaches that can be used to identify neurobiological mechanisms underlying the contributions of DSs to drug relapse.

Reward shifts in forced-choice and free-choice autoshaping with rats.

Successive negative contrast (SNC) involves a disruption of behavior when the paired reward is unexpectedly reduced from a large to a small amount, relative to a control always receiving the small amount. Five experiments with rats explored SNC in the Pavlovian autoshaping procedure in which a retractable lever is paired with the delivery of food pellets. In Experiment 1, a 12-to-2 pellet downshift either early in training (after 3 sessions) or late in training (after 20 sessions) yielded no significant evidence of SNC either in terms of lever pressing or goal entries. Experiment 2 showed that presession feeding (another form of reward devaluation) suppressed lever pressing in nonreinforced tests early in training. However, no statistical evidence of lever pressing suppression was found late in training. Presession feeding also suppressed lever pressing late in training if the test session included reinforcements. Experiment 3, using reward downshift, showed that adding a nontarget lever produced no statistical evidence of response suppression to the target lever during the downshift. Lever pressing to the target lever increased and goal entries tended to decrease after a 12-to-2 pellet downshift. Using a within-subject design and two target levers with distinct reward values (Experiment 4), reward downshift produced evidence of lever pressing enhancement in single-lever trials, but lever pressing suppression and a switch in preference to the unshifted lever in nonreinforced free-choice trials. Experiment 5 replicated these within-subject SNC effects, but found only modest evidence for a successive positive contrast effect in free-choice behavior. These results suggest that autoshaping in rats may induce response invigoration in forced-choice situations, but response suppression in free-choice situations. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

The effects of the botanical estrogen, isoliquiritigenin on delayed spatial alternation

Age-related declines in cognitive function can impair working memory, reduce speed of processing, and alter attentional resources. In particular, menopausal women may show an acceleration in the rate of cognitive decline as well as an increased vulnerability to brain diseases as estrogens may play a neuroprotective and neurotrophic role in the brain. To treat menopausal symptoms, many women turn to botanical estrogens that are promoted as a safe and natural alternative to traditional hormone replacement therapy. However, the majority of these compounds have not been systematically evaluated for efficacy and safety. The current study investigated the efficacy of the commercially available botanical estrogenic compound isoliquiritigenin (ISL) to alter performance on an operant working memory task, delayed spatial alternation (DSA). ISL is a compound found in licorice root that has been shown to have a wide range of effects on different biological systems, including estrogenic properties. This botanical is currently being used in over the counter dietary supplements. Middle-aged (12-month old) Long-Evans female rats were ovariectomized and orally dosed with either 0 mg, 6 mg, 12 mg or 24 mg of ISL 60 min before testing on the DSA task. The DSA task required the rat to alternate its responses between two retractable levers in order to earn food rewards. Random delays of 0, 3, 6, 9 or 18 s were imposed between opportunities to press. ISL treatment failed to alter DSA performance. Previous work from our research group has found that estrogenic compounds, including 17β-estradiol and the botanical estrogen genistein impair performance on the DSA task. The goal of our botanical estrogens research is to find compounds that offer some of the beneficial effects of estrogen supplementation, without the harmful effects. This work suggests that ISL may not carry the cognitive risks associated with most other estrogenic compounds tested to date.

Adrenergic manipulation inhibits pavlovian conditioned approach behaviors

Environmental rewards and Pavlovian reward cues can acquire incentive salience, thereby eliciting incentive motivational states and instigate reward-seeking. In rats, the incentive salience of food cues can be measured during a Pavlovian conditioned approach paradigm, in which rats engage in cue-directed approach (“sign-tracking”) or approach the food delivery location (“goal-tracking”). While it has been shown that dopamine signaling is necessary for sign-tracking, some studies have suggested that norepinephrine is involved in learning to sign-track as well. Thus, in order to investigate the influence of norepinephrine in Pavlovian conditioned approach, we administered three adrenergic drugs while rats learned that a food cue (an illuminated, retractable lever) preceded the delivery of banana-flavored food pellets into a food-cup. We found that pre-session injections of disulfiram (a dopamine-β-hydroxylase inhibitor) inhibited the development of sign-tracking, but goal-tracking was only affected at the high dose. In one experiment, post-session injections of disulfiram blocked the development of sign-tracking, although this effect was not replicated in a separate set of rats. Post-session injections of prazosin (an α1-adrenergic receptor antagonist) and propranolol (a β-adrenergic receptor antagonist) also blocked the development of sign-tracking but not goal-tracking. Taken together, these results suggest that adrenergic transmission mediates the acquisition of sign-tracking but not goal-tracking, and thus plays a selective role in the attribution of incentive salience food cues.

Mu opioid receptor signaling in the nucleus accumbens shell increases responsiveness of satiety-modulated lateral hypothalamus neurons.

Opioid signaling in the nucleus accumbens shell (sNAcc) has been implicated in hedonic feeding and binge eating behavior. The sNAcc projects to the lateral hypothalamus (LH), and this pathway has been suggested to modulate palatability-driven feeding behavior. In this study, we investigated the effects of sNAcc mu opioid receptor (MOR) stimulation on firing rates of LH neurons in previously sated rats. Neural firing in the LH was recorded while food-deprived rats performed an operant task to obtain sweetened Intralipid (a 4% fat emulsion containing 5% sucrose) before and after bilateral sNAcc infusion of either a MOR agonist [D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) or a saline control solution. During sessions in which saline was infused into the sNAcc, the number of trials completed after infusion were significantly lower than the number completed before infusion, likely reflecting animals' increased satiety state. During sessions in which DAMGO was infused into the sNAcc, the decrease in the number of trials completed (comparing post- vs. pre-infusion trials) was significantly attenuated. Electrophysiological recording showed that the percentage of LH neurons showing an excitatory response due to behavioral events (cue presentation, lever press, lever retraction, and consumption) was reduced in post vs. pre-saline infusion period. However, the percentage of LH neurons showing excitatory responses to the same behavioral events was similar in pre- and post-DAMGO infusion periods. These findings suggest that MOR stimulation in sNAcc leads to an increase in stimulus-evoked excitatory signaling in LH neurons which could contribute to preventing satiety-induced decline in palatable food intake.

Effects of shifts in food reinforcement context on rats' consumption of concurrently available water or sucrose solution.

The purpose of this study was to investigate the effects of signaled transitions from relatively rich to lean conditions of food reinforcement on drinking concurrently available water or sucrose-sweetened water in rats. Past research demonstrated that these negative incentive shifts produce behavioral disruption in the form of extended pausing on fixed-ratio schedules. Four male Long-Evans rats operated on a two-component multiple fixed-ratio fixed-ratio schedule. In one manipulation, the ratio was held constant and the components arranged either a large six-pellet reinforcer (rich) or small one-pellet reinforcer (lean). In a second manipulation, the components both produced a one-pellet reinforcer but differed in terms of the ratio requirement, with the rich and lean conditions corresponding to relatively small and large ratios. In both manipulations, components were pseudorandomly presented to arrange four transitions signaled by retractable levers: lean-to-lean, lean-to-rich, rich-to-rich, and rich-to-lean (the negative incentive shift). During experimental conditions, a bottle with lickometer was inserted in the chamber, providing concurrent access either to tap water or a 10% sucrose solution. The negative incentive shift produced considerably more drinking than the other transitions in all rats during both manipulations. The level of drinking was not polydipsic; rather, it appears that the negative incentive shift enhanced the value of concurrently available reinforcers relative to food reinforcement.

Individual Differences in the Attribution of Incentive Salience to a Pavlovian Alcohol Cue.

Individual differences exist in the attribution of incentive salience to conditioned stimuli associated with food. Here, we investigated whether individual differences also manifested with a Pavlovian alcohol conditioned stimulus (CS). We compiled data from five experiments that used a Pavlovian autoshaping paradigm and tests of conditioned reinforcement. In all experiments, male, Long-Evans rats with unrestricted access to food and water were acclimated to 15% ethanol. Next, rats received Pavlovian autoshaping training, in which a 10 s presentation of a retractable lever served as the CS and 0.2 mL of 15% ethanol served as the unconditioned stimulus (US). Finally, rats underwent conditioned reinforcement tests in which nose-pokes to an active aperture led to brief presentations of the lever-CS, but nose-pokes to an inactive aperture had no consequence. Rats were categorized as sign-trackers, goal-trackers and intermediates based on a response bias score that reflected their tendencies to sign-track or goal-track at different times during training. We found that distinct groups of rats either consistently interacted with the lever-CS (“sign-trackers”) or routinely approached the port during the lever-CS (“goal-trackers”) across a majority of the training sessions. However, some individuals (“shifted sign-trackers”) with an early tendency to goal-track later shifted to comparable asymptotic levels of sign-tracking as the group identified as sign-trackers. The lever-CS functioned as a conditioned reinforcer for sign-trackers and shifted sign-trackers, but not for goal-trackers. These results provide evidence of robust individual differences in the extent to which a Pavlovian alcohol cue gains incentive salience and functions as a conditioned reinforcer.

Method for testing sustained attention in touchscreen operant chambers in rats

BackgroundSustained attention, the ability to detect rare and unpredictable events, is central to cognitive performance. This construct can be tested in rodents using a Sustained Attention Task (SAT), where rats are trained to detect an unpredictably occurring signal (a brief light presentation) from non-signal events. The traditional version of this task utilizes an operant chamber with a central panel light for the signal and two retractable response levers. Adaptation of SAT to the increasingly popular touchscreen operant chambers, which do not have levers or fixed lights, could enhance the versatility of the task. New methodHere we developed a touchscreen version of SAT where the light signal is presented in the center of the touchscreen, followed by a tone to indicate the beginning of the response period. Rats indicate their choice during this period by touching their nose to one of two touchscreen response areas. The remaining parameters were kept similar to the traditional version. ResultsRats acquired touchscreen SAT at a similar rate to the traditional version. As with the traditional version, shorter stimulus durations on the signaled trials reduced accuracy and the presence of a distractor (a flashing houselight) disrupted performance on the touchscreen version. Comparison to existing methodCollectively, these data suggest that the touchscreen version is comparable to the traditional version of the SAT, and is an equally valid way of measuring sustained attention. ConclusionsMany researchers with touchscreen chambers could easily implement our modifications in order to study sustained attention.

Cooperation in rats playing the iterated Prisoner's Dilemma game

Humans and animals show cooperative behaviour, but our understanding of cooperation among unrelated laboratory animals is limited. A classic test of cooperation is the iterated Prisoner's Dilemma (IPD) game, where two players receive varying payoffs for cooperation or defection in repeated trials. To determine whether unrelated rats cooperate in the IPD, we tested pairs of rats making operant responses to earn food reward in 25 trials/day. The operant chamber was bisected by a metal screen with a retractable lever and pellet dispenser on each side. When levers extended, rats had 2 s to respond. Mutual cooperation (Reward) delivered three pellets each, mutual defection (Punishment) provided no pellets, and unilateral defection (Temptation) gave five pellets to the defector, while the partner (Sucker) received none. In eight pairs of males (RM-) and females (RF-), cooperation was defined by withholding a response. In seven pairs of RM+ males, cooperation was defined by responding on the lever. In males, food restriction significantly inhibited both cooperation and pellets received. There was no effect of dominance status. Males and females made similar numbers of responses under ad libitum feeding. However, neither food restriction nor dominance status affected responses in females. Rats were subsequently tested for reciprocity in 24 alternating trials/day. A response on the lever within 5 s delivered three pellets to the partner. Females made significantly more responses for their cage-mate than males. Responses within pairs were significantly correlated for males, but not for females. For both sexes, responses declined significantly when paired with an unfamiliar partner who never reciprocated ('bad stooge'). These results demonstrate that rats working for food show cooperation in IPD and direct reciprocity. Their responses depend on food availability and responses of their partner.

Rats that sign-track are resistant to Pavlovian but not instrumental extinction

Individuals vary in the extent to which they attribute incentive salience to a discrete cue (conditioned stimulus; CS) that predicts reward delivery (unconditioned stimulus; US), which results in some individuals approaching and interacting with the CS (sign-trackers; STs) more than others (goal-trackers; GTs). Here we asked how periods of non-reinforcement influence conditioned responding in STs vs. GTs, in both Pavlovian and instrumental tasks. After classifying rats as STs or GTs by pairing a retractable lever (the CS) with the delivery of a food pellet (US), we introduced periods of non-reinforcement, first by simply withholding the US (i.e., extinction training; experiment 1), then by signaling alternating periods of reward (R) and non-reward (NR) within the same session (experiments 2 and 3). We also examined how alternating R and NR periods influenced instrumental responding for food (experiment 4). STs and GTs did not differ in their ability to discriminate between R and NR periods in the instrumental task. However, in Pavlovian settings STs and GTs responded to periods of non-reward very differently. Relative to STs, GTs very rapidly modified their behavior in response to periods of non-reward, showing much faster extinction and better and faster discrimination between R and NR conditions. These results highlight differences between Pavlovian and instrumental extinction learning, and suggest that if a Pavlovian CS is strongly attributed with incentive salience, as in STs, it may continue to bias attention toward it, and to facilitate persistent and relatively inflexible responding, even when it is no longer followed by reward.

The attribution of incentive salience to Pavlovian alcohol cues: a shift from goal-tracking to sign-tracking.

Environmental stimuli that are reliably paired with alcohol may acquire incentive salience, a property that can operate in the use and abuse of alcohol. Here we investigated the incentive salience of Pavlovian alcohol cues using a preclinical animal model. Male, Long-Evans rats (Harlan) with unrestricted access to food and water were acclimated to drinking 15% ethanol (v/v) in their home-cages. Rats then received Pavlovian autoshaping training in which the 10 s presentation of a retractable lever served as the conditioned stimulus (CS) and 15% ethanol served as the unconditioned stimulus (US) (0.2 ml/CS; 12 CS presentations/session; 27 sessions). Next, in an operant test of conditioned reinforcement, nose pokes into an active aperture delivered presentations of the lever-CS, whereas nose pokes into an inactive aperture had no consequences. Across initial autoshaping sessions, goal-tracking behavior, as measured by entries into the fluid port where ethanol was delivered, developed rapidly. However, with extended training goal-tracking diminished, and sign-tracking responses, as measured by lever-CS activations, emerged. Control rats that received explicitly unpaired CS and US presentations did not show goal-tracking or sign-tracking responses. In the test for conditioned reinforcement, rats with CS-US pairings during autoshaping training made more active relative to inactive nose pokes, whereas rats in the unpaired control group did not. Moreover, active nose pokes were positively correlated with sign-tracking behavior during autoshaping. Extended training may produce a shift in the learned properties of Pavlovian alcohol cues, such that after initially predicting alcohol availability they acquire robust incentive salience.

Sign-tracking predicts increased choice of cocaine over food in rats

The purpose of this study was to determine whether the tendency to sign-track to a food cue was predictive of rats’ choice of cocaine over food. First, rats were trained on a procedure where insertion of a retractable lever was paired with food. A sub-group of rats – sign-trackers – primarily approached and contacted the lever, while another sub-group – goal-trackers – approached the site of food delivery. Rats were then trained on a choice task where they could choose between an infusion of cocaine (1.0mg/kg) and a food pellet (45mg). Sign-trackers chose cocaine over food significantly more often than did goal-trackers. These results support the incentive-salience theory of addiction and add to a growing number of studies which suggest that sign-trackers may model an addiction-prone phenotype.