Effects of predictive and incentive value manipulation on sign- and goal-tracking behavior.

When a neutral stimulus is repeatedly paired with an appetitive reward, two different types of conditioned approach responses may develop: a sign-tracking response directed toward the neutral cue, or a goal-tracking response directed toward the location of impending reward delivery. Sign-tracking responses have been postulated to result from attribution of incentive value to conditioned cues, while goal-tracking reflects the assignment of only predictive value to the cue. We therefore hypothesized that sign-tracking rats would be more sensitive to manipulations of incentive value, while goal-tracking rats would be more responsive to changes in the predictive value of the cue.

Nicotinic and muscarinic acetylcholine receptor antagonism dose-dependently decreases sign- but not goal-tracking behavior in male rats.

Rationale: Acetylcholinergic antagonists have shown some promise in reducing addiction-related behaviors in both preclinical and clinical studies. However, the psychological mechanisms by which these drugs are able to affect addictive behavior remain unclear. A particular key process for the development of addiction is the attribution of incentive salience to reward-related cues, which can be specifically measured in animals using a Pavlovian conditioned approach procedure.

Genetic characterization of outbred Sprague Dawley rats and utility for genome-wide association studies.

Sprague Dawley (SD) rats are among the most widely used outbred laboratory rat populations. Despite this, the genetic characteristics of SD rats have not been clearly described, and SD rats are rarely used for experiments aimed at exploring genotype-phenotype relationships. In order to use SD rats to perform a genome-wide association study (GWAS), we collected behavioral data from 4,625 SD rats that were predominantly obtained from two commercial vendors, Charles River Laboratories and Harlan Sprague Dawley Inc.

Individual variation in the attribution of incentive salience to social cues.

Research on the attribution of incentive salience to drug cues has furthered our understanding of drug self-administration in animals and addiction in humans. The influence of social cues on drug-seeking behavior has garnered attention recently, but few studies have investigated how social cues gain incentive-motivational value. In the present study, a Pavlovian conditioned approach (PCA) procedure was used to identify rats that are more (sign-trackers; STs) or less (goal-trackers; GTs) prone to attribute incentive salience to food reward cues.

Sign-tracking behavior is difficult to extinguish and resistant to multiple cognitive enhancers.

The attribution of incentive-motivational value to drug-related cues underlies relapse and craving in drug addiction. One method of addiction treatment, cue-exposure therapy, utilizes repeated presentations of drug-related cues in the absence of drug (i.e.

Single prolonged stress decreases sign-tracking and cue-induced reinstatement of cocaine-seeking.

Exposure to prolonged, uncontrollable stress reduces reward-seeking behavior, resulting in anhedonia in neuropsychiatric disorders, such as posttraumatic stress disorder. However, it is unclear to what degree stressed subjects lose interest in rewards themselves or in reward-related cues that instigate reward-seeking behavior. In the present study, we investigated the effects of single prolonged stress (SPS) on cue-directed behavior in two different procedures: Pavlovian conditioned approach (PCA) and cue-induced reinstatement of cocaine-seeking.

Thalamic mast cell activity is associated with sign-tracking behavior in rats.

Mast cells are resident immune cells in the thalamus that can degranulate and release hundreds of signaling molecules (i.e., monoamines, growth factors, and cytokines) both basally and in response to environmental stimuli.

Lesions of the ventral hippocampus attenuate the acquisition but not expression of sign-tracking behavior in rats.

Individual variation in the attribution of motivational salience to reward-related cues is believed to underlie addiction vulnerability. Pavlovian conditioned approach measures individual variation in motivational salience by identifying rats that are attracted to and motivated by reward cues (sign-trackers) or motivationally fixed on the reward itself (goal-trackers). Previously, it has been demonstrated that sign-trackers are more vulnerable to addiction-like behavior.

Subanesthetic ketamine decreases the incentive-motivational value of reward-related cues.

The attribution of incentive-motivational value to reward-related cues contributes to cue-induced craving and relapse in addicted patients. Recently, it was demonstrated that subanesthetic ketamine increases motivation to quit and decreases cue-induced craving in cocaine-dependent individuals. Although the underlying mechanism of this effect is currently unknown, one possibility is that subanesthetic ketamine decreases the incentive-motivational value of reward-related cues.

Pavlovian Conditioned Approach Training in Rats.

Cues that are contingently paired with unconditioned, rewarding stimuli can acquire rewarding properties themselves through a process known as the attribution of incentive salience, or the transformation of neutral stimuli into attractive, "wanted' stimuli capable of motivating behavior. Pavlovian conditioned approach (PCA) develops after the response-independent presentation of a conditioned stimulus (CS; e.g.

Sign-trackers have elevated myo-inositol in the nucleus accumbens and ventral hippocampus following Pavlovian conditioned approach.

Pavlovian conditioned approach (PCA) is a behavioral procedure that can be used to assess individual differences in the addiction vulnerability of drug-naïve rats and identify addiction vulnerability factors. Using proton magnetic resonance spectroscopy ( H-MRS) ex vivo, we simultaneously analyzed concentrations of multiple neurochemicals throughout the mesocorticolimbic system 2 weeks after PCA training in order to identify potential vulnerability factors to addiction in drug-naïve rats for future investigations. Levels of myo-inositol (Ins), a H-MRS-detectable marker of glial activity/proliferation, were increased in the nucleus accumbens (NAc) and ventral hippocampus, but not dorsal hippocampus or medial prefrontal cortex, of sign-trackers compared to goal-trackers or intermediate responders.

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.

Stress-free automatic sleep deprivation using air puffs.

Background: Sleep deprivation via gentle handling is time-consuming and personnel-intensive.

New Method: We present here an automated sleep deprivation system via air puffs. Implanted EMG and EEG electrodes were used to assess sleep/waking states in six male Sprague-Dawley rats.

Variation in the form of Pavlovian conditioned approach behavior among outbred male Sprague-Dawley rats from different vendors and colonies: sign-tracking vs. goal-tracking.

Even when trained under exactly the same conditions outbred male Sprague-Dawley (SD) rats vary in the form of the Pavlovian conditioned approach response (CR) they acquire. The form of the CR (i.e.

Unconditioned freezing is enhanced in an appetitive context: implications for the contextual dependency of unconditioned fear.

It has been well established that expression of conditioned fear is context independent, but the context dependency of unconditioned fear expression has rarely been explored. A recent study reported that unconditioned freezing in rats is enhanced in a familiar context, which suggests that unconditioned fear expression can be modulated by contextual processing. In order to further explore this possibility we examined unconditioned freezing in novel, familiar, and appetitive contexts; and attempted to identify brain regions critical for context-related changes in unconditioned freezing by measuring c-Fos mRNA levels in emotional circuits.

Single prolonged stress disrupts retention of extinguished fear in rats.

Clinical research has linked post-traumatic stress disorder (PTSD) with deficits in fear extinction. However, it is not clear whether these deficits result from stress-related changes in the acquisition or retention of extinction or in the regulation of extinction memories by context, for example. In this study, we used the single prolonged stress (SPS) animal model of PTSD and fear conditioning procedures to examine the effects of prior traumatic stress on the acquisition, retention, and context-specificity of extinction.

The Role of Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Cognition.

Striatal-enriched protein tyrosine phosphatase (STEP) has recently been implicated in several neuropsychiatric disorders with significant cognitive impairments, including Alzheimer's disease, schizophrenia, and fragile X syndrome. A model has emerged by which STEP normally opposes the development of synaptic strengthening and that disruption in STEP activity leads to aberrant synaptic function. We review the mechanisms by which STEP contributes to the etiology of these and other neuropsychiatric disorders.

Inactivation of the prelimbic cortex enhances freezing induced by trimethylthiazoline, a component of fox feces.

Previous research has demonstrated that the rodent medial prefrontal cortex (mPFC) is critical for the expression of unconditioned defense behaviors. The prelimbic (PL) and infralimbic (IL) cortices comprise the majority of the mPFC, but the role of these regions in mediating unconditioned defense behaviors is not well understood. In order to address this, we temporarily inactivated the PL or IL and documented the effects of these manipulations on freezing induced by trimethylthiazoline (TMT), a component of fox feces, and center region avoidance in the open field (OF).