Effects of Adolescent Caffeine Consumption on Addictive Behaviors in Adulthood

Caffeine is found in a variety of beverages such as soda, coffee, and tea, which are consumed by many people on a daily basis. Because of how commonly caffeine is consumed, it is important to discover the effects adolescent caffeine consumption may have on adult addiction behaviors. A rat model was used to explore the potential effects of adolescent caffeine consumption. Rats consumed caffeine during their adolescent period and underwent behavioral tests in adulthood to assess whether they displayed behaviors associated with enhanced vulnerability to drug addiction. Behavioral tests used to assess addictive behaviors in adulthood included drug self-administration (SA) and a Pavlovian Conditioned Approach (PCA) task. Our findings show that rats that consume caffeine during adolescence self-administer cocaine in adulthood at a higher rate than controls. Rats consuming caffeine during adolescence also have a higher breakpoint for cocaine self-administration in adulthood than controls, indicating that adolescent caffeine consumption increases motivation for drug taking. We also found that a greater percentage of rats consuming caffeine during early adolescence displayed “sign-tracking” behaviors during the PCA task that has been associated with altered dopamine signaling and correlated with increased drug self-administration. While the results were not as clear, a similar trend was also seen in rats that consumed caffeine during their late adolescent period. Overall, these findings illustrate that adolescent caffeine consumption enhances addictive behaviors in adulthood

The nature of phenotypic variation in Pavlovian conditioning

Pavlovian conditioning procedures result in dramatic individual differences in the topography of learnt behaviors in rats: When the temporary insertion of a lever into an operant chamber is paired with food pellets, some rats (known as sign-trackers) predominantly interact with the lever, while others (known as goal-trackers) predominantly approach the food well. Two experiments examined the sensitivity of these two behaviors to changing reinforcement contingencies in groups of males and female rats exhibiting the different phenotypes (i.e., sign-trackers and goal-trackers). In both phenotypes, behavior oriented to the food well was more sensitive to contingency changes (e.g., a reversal in which of two levers was reinforced) than was lever-oriented behavior. That is, the nature of the two behaviors differed independently of the rats in which they were manifest. These results indicate that the behavioral phenotypes reflect the parallel operation of a stimulus-stimulus associative process that gives rise to food-well activity and a stimulus-response process that gives rise to leveroriented activity, rather than the operation of a single process (e.g., stimulus-stimulus) that generates both behaviors

Animal models of maladaptive traits: disorders in sensorimotor gating and attentional quantifiable responses as possible endophenotypes

Traditional diagnostic scales are based on a number of symptoms to evaluate and classify mental diseases. In many cases, this process becomes subjective, since the patient must calibrate the magnitude of his/her symptoms and therefore the severity of his/her disorder. A completely different approach is based on the study of the more vulnerable traits of cognitive disorders. In this regard, animal models of mental illness could be a useful tool to characterize indicators of possible cognitive dysfunctions in humans. Specifically, several cognitive disorders such as schizophrenia involve a dysfunction in the mesocorticolimbic dopaminergic system during development. These variations in dopamine levels or dopamine receptor sensibility correlate with many behavioral disturbances. These behaviors may be included in a specific phenotype and may be analyzed under controlled conditions in the laboratory. The present study provides an introductory overview of different quantitative traits that could be used as a possible risk indicator for different mental disorders, helping to define a specific endophenotype. Specifically, we examine different experimental procedures to measure impaired response in attention linked to sensorimotor gating as a possible personality trait involved in maladaptive behaviors.Ministerio de Economía y Competitividad PSI2012- 3244

Individual variation in incentive salience attribution and accumbens dopamine transporter expression and function

Cues (conditioned stimuli; CSs) associated with rewards can come to motivate behavior, but there is considerable individual variation in their ability to do so. For example, a lever-CS that predicts food reward becomes attractive, wanted, and elicits reward-seeking behavior to a greater extent in some rats (“sign-trackers”; STs), than others (“goal-trackers”; GTs). Variation in dopamine (DA) neurotransmission in the nucleus accumbens (NAc) core is thought to contribute to such individual variation. Given that the DA transporter (DAT) exerts powerful regulation over DA signaling, we characterized the expression and function of the DAT in the accumbens of STs and GTs. STs showed greater DAT surface expression in ventral striatal synaptosomes than GTs, and ex vivo fast-scan cyclic voltammetry recordings of electrically-evoked DA release confirmed enhanced DAT function in STs, as indicated by faster DA uptake, specifically in the NAc core. Consistent with this, systemic amphetamine (AMPH) produced greater inhibition of DA uptake in STs than in GTs. Furthermore, injection of AMPH directly into the NAc core enhanced lever-directed approach in STs, presumably by amplifying the incentive value of the CS, but had no effect on goal tracking behavior. On the other hand, there were no differences between STs and GTs in electrically-evoked DA release in slices, or in total ventral striatal DA content. We conclude that greater DAT surface expression may facilitate the attribution of incentive salience to discrete reward cues. Investigating this variability in animal sub-populations may help explain why some people abuse drugs, while others do not

Human sign- and goal-trackers detected using a simple Pavlovian device: Differences in self-reported impulsivity and addictive tendencies

Honors (Bachelor's)NeuroscienceUniversity of Michiganhttp://deepblue.lib.umich.edu/bitstream/2027.42/112153/1/schwankj.pd

Sex-dependent associations between addiction-related behaviors and the microbiome in outbred rats.

BackgroundMultiple factors contribute to the etiology of addiction, including genetics, sex, and a number of addiction-related behavioral traits. One behavioral trait where individuals assign incentive salience to food stimuli ("sign-trackers", ST) are more impulsive compared to those that do not ("goal-trackers", GT), as well as more sensitive to drugs and drug stimuli. Furthermore, this GT/ST phenotype predicts differences in other behavioral measures. Recent studies have implicated the gut microbiota as a key regulator of brain and behavior, and have shown that many microbiota-associated changes occur in a sex-dependent manner. However, few studies have examined how the microbiome might influence addiction-related behaviors. To this end, we sought to determine if gut microbiome composition was correlated with addiction-related behaviors determined by the GT/ST phenotype.MethodsOutbred male (N=101) and female (N=101) heterogeneous stock rats underwent a series of behavioral tests measuring impulsivity, attention, reward-learning, incentive salience, and locomotor response. Cecal microbiome composition was estimated using 16S rRNA gene amplicon sequencing. Behavior and microbiome were characterized and correlated with behavioral phenotypes. Robust sex differences were observed in both behavior and microbiome; further analyses were conducted within sex using the pre-established goal/sign-tracking (GT/ST) phenotype and partial least squares differential analysis (PLS-DA) clustered behavioral phenotype.ResultsOverall microbiome composition was not associated to the GT/ST phenotype. However, microbial alpha diversity was significantly decreased in female STs. On the other hand, a measure of impulsivity had many significant correlations to microbiome in both males and females. Several measures of impulsivity were correlated with the genus Barnesiella in females. Female STs had notable correlations between microbiome and attentional deficient. In both males and females, many measures were correlated with the bacterial families Ruminocococcaceae and Lachnospiraceae.ConclusionsThese data demonstrate correlations between several addiction-related behaviors and the microbiome specific to sex

Sign Tracking and Goal Tracking Are Characterized by Distinct Patterns of Nucleus Accumbens Activity

During Pavlovian conditioning, if a cue (e.g., lever extension) predicts reward delivery in a different location (e.g., a food magazine), some individuals will come to approach and interact with the cue, a behavior known as sign tracking (ST), and others will approach the site of reward, a behavior known as goal tracking (GT). In rats, the acquisition of ST versus GT behavior is associated with distinct profiles of dopamine release in the nucleus accumbens (NAc), but it is unknown whether it is associated with different patterns of accumbens neural activity. Therefore, we recorded from individual neurons in the NAc core during the acquisition, maintenance, and extinction of ST and GT behavior. Even though NAc dopamine is specifically important for the acquisition and expression of ST, we found that cue-evoked excitatory responses encode the vigor of both ST and GT behavior. In contrast, among sign trackers only, there was a prominent decrease in reward-related activity over the course of training, which may reflect the decreasing reward prediction error encoded by phasic dopamine. Finally, both behavior and cue-evoked activity were relatively resistant to extinction in sign trackers, as compared with goal trackers, although a subset of neurons in both groups retained their cue-evoked responses. Overall, the results point to the convergence of multiple forms of reward learning in the NAc

Resting-state brain activation patterns and network topology distinguish human sign and goal trackers

The “Sign-tracker/Goal-tracker” (ST/GT) is an animal model of individual differences in learning and motivational processes attributable to distinctive conditioned responses to environmental cues. While GT rats value the reward-predictive cue as a mere predictor, ST rats attribute it with incentive salience, engaging in aberrant reward-seeking behaviors that mirror those of impulse control disorders. Given its potential clinical value, the present study aimed to map such model onto humans and investigated resting state functional magnetic resonance imaging correlates of individuals categorized as more disposed to sign-tracking or goal-tracking behavior. To do so, eye-tracking was used during a translationally informed Pavlovian paradigm to classify humans as STs (n = 36) GTs (n = 35) or as Intermediates (n = 33), depending on their eye-gaze towards the reward-predictive cue or the reward location. Using connectivity and network-based approach, measures of resting state functional connectivity and centrality (role of a node as a hub) replicated preclinical findings, suggesting a major involvement of subcortical areas in STs, and dominant cortical involvement in GTs. Overall, the study strengthens the translational value of the ST/GT model, with important implications for the early identification of vulnerable phenotypes for psychopathological conditions such as substance use disorder

The observation of cue-directed behavior in sign-tracking and goal-tracking rats following implantation of designer receptors

Increasing evidence that ordinary cues paired with reward can acquire value indicates that the incentive properties of rewards are capable of being transferred onto cues, making them incentive stimuli. Studies have begun focusing on isolating components of the reward circuit involved in imparting incentive salience onto a cue with the goal of identifying rats with susceptibilities to drug addiction. Such studies have found that under a Pavlovian Conditioned Approach (PCA) paradigm, sign-tracking rats are at increased risk for instilling incentive salience onto conditioned stimuli and for engaging in drug-related behavior. With better understanding of the neural basis of sign tracking and its behavioral aspect of drug seeking comes a better chance of discovering treatment methods for drug addiction. This study examines the potential behavioral outcomes of altering the pathway starting in the Ventral Pallidum (VP) and ending in the Ventral Tegmental Area (VTA) by using Designer Receptors Exclusively Activated by Designer Drugs (DREADDs). While there is some evidence of an interaction between the effects of DREADDs on this neural circuit and behavior, not all results presented here reach significance. Additional studies are needed to confirm the hypothesis of specific inhibitory DREADDs from the VP to the VTA causing increased amounts of sign tracking in rats as a way to assess whether this pathway is implicated in predisposing rats to sign-tracking behavior.2018-07-11T00:00:00