Doctor of Philosophy (Phd) / Despite an abundance of evidence demonstrating that the temporal relationship between events is a key factor in an organism learning an association between those events, a general theoretical account of temporal contiguity has remained elusive. A particular question that has received little attention is whether behaviour established with strong contiguity can be maintained when contiguity is weakened. The primary aims of this thesis were to examine the mechanisms underlying both the effects of contiguity on learning in rats and humans and the maintenance effect described above. The experiments reported in this thesis demonstrated that rats’ lever-pressing for food/sucrose acquired with immediate reinforcement persisted when a trace/delay that would have prevented acquisition was subsequently introduced, provided the lever was a valid signal for reinforcement. In classical conditioning with a 10-second trace, rats performed magazine-entry during lever-insertion (goal-tracking) instead of lever-pressing (sign-tracking); with zero-trace, rats both sign- and goal-tracked if lever-insertion time was 10 seconds, while goal-tracking dominated with 5-second lever-insertion time. Furthermore, while it was found that context-US associations may interfere with CS-US learning, context conditioning did not contribute to the retardation of sign-tracking in trace conditioning. Overall, these results are consistent with the theory that a localisable manipulandum that signals an appetitive outcome with strong contiguity acquires hedonic value, and that such hedonic value drives lever-pressing behaviour that is resistant to changes in the conditions of reinforcement. Human performance in a conditioned suppression task was inversely related to trace interval, but this apparent contiguity effect was at least partially mediated by the number of distractors during the trace interval, as predicted by Revusky’s concurrent interference theory. Furthermore, some transfer of conditioned suppression was observed when the trace was subsequently lengthened. Despite the different explanations proposed to account for rat and human performance in these experiments, the results suggest that the effects of contiguity on learning may be driven by similar underlying mechanisms across species.

Doctor of Philosophy (Phd) / Despite an abundance of evidence demonstrating that the temporal relationship between events is a key factor in an organism learning an association between those events, a general theoretical account of temporal contiguity has remained elusive. A particular question that has received little attention is whether behaviour established with strong contiguity can be maintained when contiguity is weakened. The primary aims of this thesis were to examine the mechanisms underlying both the effects of contiguity on learning in rats and humans and the maintenance effect described above. The experiments reported in this thesis demonstrated that rats’ lever-pressing for food/sucrose acquired with immediate reinforcement persisted when a trace/delay that would have prevented acquisition was subsequently introduced, provided the lever was a valid signal for reinforcement. In classical conditioning with a 10-second trace, rats performed magazine-entry during lever-insertion (goal-tracking) instead of lever-pressing (sign-tracking); with zero-trace, rats both sign- and goal-tracked if lever-insertion time was 10 seconds, while goal-tracking dominated with 5-second lever-insertion time. Furthermore, while it was found that context-US associations may interfere with CS-US learning, context conditioning did not contribute to the retardation of sign-tracking in trace conditioning. Overall, these results are consistent with the theory that a localisable manipulandum that signals an appetitive outcome with strong contiguity acquires hedonic value, and that such hedonic value drives lever-pressing behaviour that is resistant to changes in the conditions of reinforcement. Human performance in a conditioned suppression task was inversely related to trace interval, but this apparent contiguity effect was at least partially mediated by the number of distractors during the trace interval, as predicted by Revusky’s concurrent interference theory. Furthermore, some transfer of conditioned suppression was observed when the trace was subsequently lengthened. Despite the different explanations proposed to account for rat and human performance in these experiments, the results suggest that the effects of contiguity on learning may be driven by similar underlying mechanisms across species.

A devastating feature of drug-dependence is the susceptibility of relapse (40-60%) after stretches of abstinence. One theory that may account for relapse suggests that drug cues (e.g., paraphernalia) may increase stress hormones, and this may prompt relapse. Repeatedly pairing a neutral cue with a reward is commonly utilized to measure what subjects learn about a cue that is predictive of reward. Research has shown that animals that attend to a cue more than to the reward (sign trackers) may be more vulnerable to drug addiction. Additionally, research has shown that sign tracking is associated with an increase in corticosterone (CORT), a primary stress hormone. PT 150 is a novel glucocorticoid receptor antagonist that attenuates the effects of CORT. Experiment 1 hypothesized that subjects given repeated oral administration of 40 mg/kg PT 150 would reduce sign tracking compared to subjects given placebo. Results of Experiment 1 showed that repeated oral consumption of 40 mg/kg PT 150 decreased sign tracking behavior compared to placebo. In Experiment 2, it was hypothesized that PT 150 (20/40/60 mg/kg) given by subcutaneous (SC) injection would reduce sign tracking dose-dependently, and that sign tracking behavior would correlate with CORT levels. Results of Experiment 2 showed that SC injection of 20 mg/kg PT 150 reduced sign tracking but not 40 or 60 mg/kg. Additionally, the correlation between CORT and the sign tracking for the 20 mg/kg approached significance. Although tentative, the correlation may suggest that elevated plasma CORT concentrations correlate with elevated sign tracking. The current findings extend the current literature by suggesting that the glucocorticoid receptor may be a potential pharmacological target for reducing relapse-like behaviors.

Pavlovian conditioned stimuli can acquire incentive motivational properties, and this phenomenon can be measured in animals using Pavlovian conditioned approach behavior. Drugs of abuse can influence the expression of this behavior, and nicotine in particular exhibits incentive amplifying effects. Both conditioned approach behavior and drug abuse rely on overlapping corticolimbic circuitry. We hypothesize that the orbitofrontal cortex (OFC) regulates conditioned approach, and that one site of nicotine action is in the OFC where it reduces cortical output. To test this, we repeatedly exposed rats to 0.4 mg/kg nicotine (s.c.) during training and then pharmacologically inactivated the lateral OFC or performed in vivo electrophysiological recordings of lateral OFC neurons in the presence or absence of nicotine. In Experiment 1, animals were trained in a Pavlovian conditioning paradigm and behavior was evaluated after inactivation of the OFC by microinfusion of the GABA agonists baclofen and muscimol. In Experiment 2, we monitored phasic firing of OFC neurons during Pavlovian conditioning sessions. Nicotine reliably enhanced conditioned responding to the conditioned cue, and inactivation of the OFC reduced conditioned responding, especially the sign-tracking response. OFC neurons exhibited phasic excitations to cue presentation and during goal tracking, and nicotine acutely blunted this phasic neuronal firing. When nicotine was withheld, both conditioned responding and phasic firing in the OFC returned to the level of controls. These results suggest that the OFC is recruited for the expression of conditioned responses, and that nicotine acutely influences this behavior by reducing phasic firing in the OFC.

Nicotine is a psychomotor stimulant with ‘reinforcement enhancing’ effects — the actions of nicotine in the brain increase responding for non-nicotine rewards. We hypothesized that this latter effect of nicotine depends on increased incentive properties of anticipatory cues; consistent with this hypothesis, multiple laboratories have reported that nicotine increases sign tracking, i.e. approach to a conditioned stimulus (CS), in Pavlovian conditioned-approach tasks. Incentive motivation and sign tracking are mediated by mesolimbic dopamine (DA) transmission and nicotine facilitates mesolimbic DA release. Therefore, we hypothesized that the incentive-promoting effects of nicotine would be impaired by DA antagonists. To test this hypothesis, separate groups of rats were injected with nicotine (0.4 mg/kg base) or saline prior to Pavlovian conditioning sessions in which a CS (30 s illumination of a light or presentation of a lever) was immediately followed by a sweet reward delivered in an adjacent location. Both saline and nicotine pretreated rats exhibited similar levels of conditioned approach to the reward location (goal tracking), but nicotine pretreatment significantly increased approach to the CS (sign tracking), regardless of type (lever or light). The DAD1 antagonist SCH-23390 and the DAD2/3antagonist eticlopride reduced conditioned approach in all rats, but specifically reduced goal tracking in the saline pretreated rats and sign tracking in the nicotine pretreated rats. The non-selective DA antagonist flupenthixol reduced sign-tracking in nicotine rats at all doses tested; however, only the highest dose of flupenthixol reduced goal tracking in both nicotine and saline groups. The reductions in conditioned approach behavior, especially those by SCH-23390, were dissociated from simple motor suppressant effects of the antagonists. These experiments are the first to investigate the effects of dopaminergic drugs on the facilitation of sign-tracking engendered by nicotine and they implicate dopaminergic systems both in conditioned approach as well as the incentive-promoting effects of nicotine.

The attribution of incentive salience to cues that become associated with drugs of abuse is a critical characteristic of individuals who may be vulnerable to drug addiction. Rodents with the propensity to sign track are thought to be vulnerable to drug abuse. The goal of the current work was to investigate whether sign trackers (STs) would acquire cocaine conditioned place preference (CPP) to a discrete cue using an avian species. In Experiment 1, sign and goal trackers (GTs) were first identified using a one third rank order split. Following identification, cocaine-CPP was conducted with a discrete cue in each end chamber. Contrary to previous research, results showed that GTs showed a CPP to the discrete cue but STs did not. Experiment 2 was conducted to determine whether sign and GTs had been misclassified with the rank order split. Experiment 2 compared the rank order method with a t-test method (absolute criterion). Misclassification of both sign and GTs occurred using the rank order split. The findings indicated that use of a more accurate method to identify sign and GTs may have led to different results for Experiment 1. The t-test method may be useful for models that require identification of STs.