The Role of the Serotonin Transporter as a Genetic Risk Factor in the Development of Drug Addiction

<p>Drug addiction is a ubiquitous phenomenon worldwide that places tremendous financial and psychological burden on societies, families and the individual. Interestingly, only a small percentage of individuals ( 20%), regardless their drug of choice, go on to develop the compulsive behaviours that define drug addiction. Clinical studies have shown that there is a subset of the population with a genetically determined reduction in the serotonin transporter that may increase vulnerability to developing a variety of psychiatric disorders like depression, anxiety and drug addiction. To investigate the influence of reduced serotonin transporter function in the laboratory we studied the effects of MDMA (‘ecstasy’) and heroin in a genetically altered animal model: the serotonin transporter (SERT) knockout rat. Homozygous (HOM) animals lack SERT function completely while heterozygous (HET) have about 50% SERT function compared to the wild type (WT). Groups of HOM, HET and WT animals completed MDMA or heroin self-administration experiments. A robust genotype effect emerged for animals self-administering MDMA; facilitation of MDMA self-administration was inversely related to SERT function. HOM animals, without exception, reached acquisition criterion significantly faster than the HET animals; HET animals then showed higher acquisition rates compared to the WT animals. In contrast, there were no differences between the genotypes when animals self-administered heroin. To investigate the driving force behind facilitated MDMA self-administration in animals with reduced SERT function locomotor activity and conditioned taste aversion experiments were undertaken. In contrast to the drug self-administration experiments,MDMA induced hyperactivity was positively related to SERT function. Thus, it was significantly reduced in HOM and HET animals compared to the WT. Again, heroin treatment did not produce differences in locomotion between the genotypes. MDMA induced conditioned taste aversion revealed only a main effect of dose with robust conditioned taste aversion for both drug doses, although a trend indicated that HOM animals may have heightened sensitivity to MDMA. However, heroin treatment failed to produce a conditioned taste aversion effect in any of the groups regardless of dose. Beyond the aforementioned behavioural experiments striatal brain tissue from the animals that had previously self-administered MDMA or heroin was analysed via quantitative reverse transcription polymerase chain reaction; five targets were evaluated to quantify drug induced changes in brain derived neurotrophic factor gene expression (BDNF). Several BDNF isoforms (total BDNF, BDNF III and BDNF IV) were significantly increased in animals that had self-administered MDMA; this effect was true across HOM, HET and WT subjects. Comparatively, animals that had self-administered heroin did not show a difference in BDNF expression compared to untreated control animals. This suite of experiments provides insight into the influence of a compromised serotonergic system on the development of drug addiction. That is, while reduced SERT function does not appear to augment the addictive properties of drugs like heroin there is reason to suspect that it does confer additional susceptibility to developing addiction to drugs like MDMA, highlighting the hypothesis that different classes of addictive substances act through different neurobiological pathways.</p>

Maintained goal-directed control with overtraining on ratio schedules

It is thought that goal-directed control of actions weakens or becomes masked by habits over time. We tested the opposing hypothesis that goal-directed control becomes stronger over time, and that this growth is modulated by the overall action–outcome contiguity. Despite group differences in action–outcome contiguity early in training, rats trained under random and fixed ratio schedules showed equivalent goal-directed control of lever pressing that appeared to grow over time. We confirmed that goal-directed control was maintained after extended training under another type of ratio schedule—continuous reinforcement—using specific satiety and taste aversion devaluation methods. These results add to the growing literature showing that extensive training does not reliably weaken goal-directed control and that it may strengthen it, or at least maintain it.

The Role of the Serotonin Transporter as a Genetic Risk Factor in the Development of Drug Addiction

<p>Drug addiction is a ubiquitous phenomenon worldwide that places tremendous financial and psychological burden on societies, families and the individual. Interestingly, only a small percentage of individuals ( 20%), regardless their drug of choice, go on to develop the compulsive behaviours that define drug addiction. Clinical studies have shown that there is a subset of the population with a genetically determined reduction in the serotonin transporter that may increase vulnerability to developing a variety of psychiatric disorders like depression, anxiety and drug addiction. To investigate the influence of reduced serotonin transporter function in the laboratory we studied the effects of MDMA (‘ecstasy’) and heroin in a genetically altered animal model: the serotonin transporter (SERT) knockout rat. Homozygous (HOM) animals lack SERT function completely while heterozygous (HET) have about 50% SERT function compared to the wild type (WT). Groups of HOM, HET and WT animals completed MDMA or heroin self-administration experiments. A robust genotype effect emerged for animals self-administering MDMA; facilitation of MDMA self-administration was inversely related to SERT function. HOM animals, without exception, reached acquisition criterion significantly faster than the HET animals; HET animals then showed higher acquisition rates compared to the WT animals. In contrast, there were no differences between the genotypes when animals self-administered heroin. To investigate the driving force behind facilitated MDMA self-administration in animals with reduced SERT function locomotor activity and conditioned taste aversion experiments were undertaken. In contrast to the drug self-administration experiments,MDMA induced hyperactivity was positively related to SERT function. Thus, it was significantly reduced in HOM and HET animals compared to the WT. Again, heroin treatment did not produce differences in locomotion between the genotypes. MDMA induced conditioned taste aversion revealed only a main effect of dose with robust conditioned taste aversion for both drug doses, although a trend indicated that HOM animals may have heightened sensitivity to MDMA. However, heroin treatment failed to produce a conditioned taste aversion effect in any of the groups regardless of dose. Beyond the aforementioned behavioural experiments striatal brain tissue from the animals that had previously self-administered MDMA or heroin was analysed via quantitative reverse transcription polymerase chain reaction; five targets were evaluated to quantify drug induced changes in brain derived neurotrophic factor gene expression (BDNF). Several BDNF isoforms (total BDNF, BDNF III and BDNF IV) were significantly increased in animals that had self-administered MDMA; this effect was true across HOM, HET and WT subjects. Comparatively, animals that had self-administered heroin did not show a difference in BDNF expression compared to untreated control animals. This suite of experiments provides insight into the influence of a compromised serotonergic system on the development of drug addiction. That is, while reduced SERT function does not appear to augment the addictive properties of drugs like heroin there is reason to suspect that it does confer additional susceptibility to developing addiction to drugs like MDMA, highlighting the hypothesis that different classes of addictive substances act through different neurobiological pathways.</p>

What Facets of Picky Eating Relate To Eating Concerns in Undergraduate Students?: The Moderating Effects of Inflexible Eating and Mental Health Concerns

Purpose: Picky eating (PE) can occur in adulthood and is associated with mental health concerns. PE is often conceptualized as distinct from disordered eating, but recent research maps positive relationships between these maladaptive eating phenotypes. Relatedly, recent research suggests PE is more strongly related to eating concerns, a facet of disordered eating, via inflexible eating and mental health concerns, but precisely what PE facets explain these relations remain unknown.Methods: A large, undergraduate sample (N=509) completed an online survey assessing PE facets (Adult Picky Eating Questionnaire; meal presentation, food variety, meal disengagement, and taste aversion), disordered eating (Eating Disorder Examination Questionnaire), specifically eating concerns, mental health concerns (Depression, Anxiety and Stress Scale - 21 Items), and inflexible eating (Inflexible Eating Questionnaire).Results: Positive relationships emerged between PE facets, eating concerns, inflexible eating, and mental health concerns. Meal disengagement was more strongly associated with eating concerns when inflexible eating was higher, whereas food variety and meal presentation were more strongly associated with eating concerns when mental health concerns was higher. Inflexible eating and mental health concerns did not significantly interact with taste aversion to explain variance in eating concerns.Conclusions: Considering PE multidimensionally may yield important insights beyond the broader construct. Mental health concerns and inflexible eating may be treatment and research targets in addressing the overlap between PE facets such as meal presentation, meal disengagement, and food variety and eating concerns. Level of Evidence: Level V, cross-sectional descriptive study.

Conditioned Taste Aversion as a Tool for Mitigating Human-Wildlife Conflicts

Modern wildlife management has dual mandates to reduce human-wildlife conflict (HWC) for burgeoning populations of people while supporting conservation of biodiversity and the ecosystem functions it affords. These opposing goals can sometimes be achieved with non-lethal intervention tools that promote coexistence between people and wildlife. One such tool is conditioned taste aversion (CTA), the application of an evolutionary relevant learning paradigm in which an animal associates a transitory illness to the taste, odor or other characteristic of a particular food item, resulting in a long-term change in its perception of palatability. Despite extensive support for the power of CTA in laboratory studies, field studies have exhibited mixed results, which erodes manager confidence in using this tool. Here we review the literature on CTA in the context of wildlife conservation and management and discuss how success could be increased with more use of learning theory related to CTA, particularly selective association, stimulus salience, stimulus generalization, and extinction of behavior. We apply learning theory to the chronological stages of CTA application in the field and illustrate them by synthesizing and reviewing past applications of CTA in HWC situations. Specifically, we discuss (1) when CTA is suitable, (2) how aversion can be most effectively (and safely) established, (3) how generalization of aversion from treated to untreated food can be stimulated and (4) how extinction of aversion can be avoided. For each question, we offer specific implementation suggestions and methods for achieving them, which we summarize in a decision-support table that might be used by managers to guide their use of CTA across a range of contexts. Additionally, we highlight promising ideas that may further improve the effectiveness of CTA field applications in the future. With this review, we aspire to demonstrate the diverse past applications of CTA as a non-lethal tool in wildlife management and conservation and facilitate greater application and efficacy in the future.

Maintained goal-directed control with overtraining on ratio schedules

It is thought that goal-directed control of actions weakens or becomes masked by habits over time. We tested the opposing hypothesis that goal-directed control becomes stronger over time, and that this growth is modulated by the overall action-outcome contiguity. Despite group differences in action-outcome contiguity early in training, rats trained under random and fixed ratio schedules showed equivalent goal-directed control of lever pressing that grew over time. We confirmed that goal-directed control was maintained over time under another type of ratio schedule—continuous reinforcement—using both specific satiety and taste aversion devaluation methods. These results add to the growing literature showing that extensive training does not always weaken goal-directed control, and can strengthen its expression.