The capability of cocaine-associated stimuli in eliciting craving in human addicts, even after extended periods of abstinence, is modeled in animals using cue reinstatement of extinguished cocaine-seeking behavior. This study aimed to examine brain activation in response to cocaine cues in this model apart from activation produced by test novelty using a novel cue control. Rats trained to self-administer cocaine paired with either an oscillating light or tone cue underwent daily extinction training and were then tested for reinstatement of extinguished cocaine-seeking behavior elicited by response-contingent presentations of either their assigned cocaine-paired cue or the alternate, novel cue. Additional controls received saline infusions and cue presentations yoked to a cocaine-trained rat. Brains were harvested for Fos immunohistochemistry immediately after the 90-min reinstatement test. Surprisingly, conditioned and novel cues both reinstated responding to a similar degree; however magnitude of reinstatement did vary by cue modality with the greatest reinstatement to the light cues. In most brain regions, Fos expression was enhanced in rats with a history of cocaine training regardless of cue type with the exception of the Cg1 region of the anterior cingulate cortex, which was sensitive to test cue modality. Also Fos expression within the dorsomedial caudate-putamen was correlated with responding in the novel, but not conditioned, cue groups. In subsequent experiments, we observed a similar pattern of reinstatement in rats trained and tested for sucrose-seeking behavior, whereas rats trained and tested with the cues only reinstated to a novel light and tone, but not a familiar cue. The results suggest that novel cues reinstate responding to a similar extent as conditioned cues regardless of whether animals have a history of operant-delivered drug or a natural reinforcer. Furthermore, similar brain circuits as those involved in cocaine-seeking behavior are activated by novel cues, suggesting converging processes exist to drive conditioned and novel reinforcement seeking.

Anxiety sensitivity (AS; the fear of anxiety-related bodily sensations) has been earmarked as a significant risk factor in the development and maintenance of pathological anxiety in adults and children. Given the potential implications of heightened AS, recent research has focused on investigating the etiology and developmental course of elevated AS; however, most of this work has been conducted with adults and is retrospective in nature. Data from college students show that early anxiety-related learning experiences may be a primary source of heightened AS levels, but it remains unclear whether AS in children is linked to their learning experiences (i.e., parental reinforcement, modeling, punishment, and/or transmission of information about anxiety-related behaviors). Based on AS theory and its iterations, an emerging theoretical model was developed to aid further exploration of the putative causes and consequences of heightened AS levels. Using a sample of 70 clinic-referred youth (ages 6 to 16 years old; 51.4% Hispanic/Latino), the present study sought to further explicate the role of learning in the development of AS and anxiety symptoms. Results suggest that childhood learning experiences may be an important precursor to heightened AS levels and, subsequently, increased experiences of anxiety symptoms. Findings also indicate that some youth may be more vulnerable to anxiety-related learning experiences and suggest that culture may play a role in the relations among learning, AS, and anxiety symptoms.

Three experiments used a spatial serial conditioning paradigm to assess the effectiveness of spatially informative conditioned stimuli in eliciting tracking behavior in pigeons. The experimental paradigm consisted of the simultaneous presentation of 2 key lights (CS2 and CTRL), followed by another key light (CS1), followed by food (the unconditioned stimulus or US). CS2 and CTRL were presented in 2 of 3 possible locations, randomly assigned; CS1 was always presented in the same location as CS2. CS2 was designed to signal the spatial, but not the temporal locus of CS1; CS1 signaled the temporal locus of the US. In Experiment 1, differential pecking on CS2 was observed even when CS2 was present throughout the interval between CS1s, but only in a minority of pigeons. A control condition verified that pecking on CS2 was not due to temporal proximity between CS2 and US. Experiment 2 demonstrated the reversibility of spatial conditioning between CS2 and CTRL. Asymptotic performance never involved tracking CTRL more than CS2 for any of 16 pigeons. It is inferred that pigeons learned the spatial association between CS2 and CS1, and that temporal contingency facilitated its expression as tracking behavior. In a third experiment, with pigeons responding to a touchscreen monitor, differential responding to CS2 was observed only when CS2 disambiguated the location of a random CS1. When the presentation location of CS1 was held constant, no differences in responding to CS2 or CTRL were observed.

The failure to withhold inappropriate behavior is a central component of most impulse control disorders, including Attention Deficit Hyperactivity Disorder (ADHD). The present study examined the effects of housing environment and methylphenidate (a drug often prescribed for ADHD) on the performance of rats in two response inhibition tasks: differential reinforcement of low rate (DRL) and fixed minimum interval (FMI). Both tasks required rats to wait a fixed amount of time (6 s) before emitting a reinforced response. The capacity to withhold the target response (volitional inhibition) and timing precision were estimated on the basis of performance in each of the tasks. Paradoxically, rats housed in a mildly enriched environment that included a conspecific displayed less volitional inhibition in both tasks compared to rats housed in an isolated environment. Enriched housing, however, increased timing precision. Acute administration of methylphenidate partially reversed the effects of enriched housing. Implications of these results in the assessment and treatment of ADHD-related impulsivity are discussed.

Nicotine is thought to underlie the reinforcing and dependence-producing effects of tobacco-containing products. Nicotine supports self-administration in rodents, although measures of its reinforcing effects are often confounded by procedures that are used to facilitate acquisition, such as food restriction, prior reinforcement training, or response-contingent co-delivery of a naturally reinforcing light. This study examined whether rats acquire nicotine self-administration in the absence of these facilitators. A new mathematical modeling procedure was used to define the criterion for acquisition and to determine dose-dependent differences in rate and asymptote levels of intake. Rats were trained across 20 daily 2-h sessions occurring 6 days/week in chambers equipped with active and inactive levers. Each active lever press resulted in nicotine reinforcement (0, 0.015, 0.03, 0.06 mg/kg, IV) and retraction of both levers for a 20-s time out, whereas inactive lever presses had no consequences. Acquisition was defined by the best fit of a logistic function (i.e., S-shaped) versus a constant function (i.e., flat line) for reinforcers obtained across sessions using a corrected Akaike information criterion (AICc) as a model selection tool. The results showed an inverted-U shaped function for dose in relation to the percentage of animals that acquired nicotine self-administration, with 46% acquiring at 0.015 mg/kg, 73% at 0.03 mg/kg, and 58% at 0.06 mg/kg. All saline rats failed to acquire as expected. For rats that acquired nicotine self-administration, multiple model comparisons demonstrated that the asymptote (highest number of reinforcers/session) and half learning point (h; session during which half the assymptote had been achieved) were justified as free parameters of the reinforcers/session function, indicating that these parameters vary with nicotine dose. Asymptote exhibited an inverted U-shaped function across doses and half learning point exhibited a negative relationship to dose (i.e., the higher the dose the fewer sessions to reach h). These findings suggest that some rats acquire nicotine self-administration without using procedures that confound measures of acquisition rate. Furthermore, the modeling approach provides a new way of defining acquisition of drug self-administration that takes advantage of using all data generated from individual subjects and is less arbitrary than some criteria that are currently used.