Altered Brain Activity during Reward Anticipation in Pathological Gambling and Obsessive-Compulsive Disorder

Background

Pathological gambling (PG) and obsessive-compulsive disorder (OCD) are conceptualized as a behavioral addiction, with a dependency on repetitive gambling behavior and rewarding effects following compulsive behavior, respectively. However, no neuroimaging studies to date have examined reward circuitry during the anticipation phase of reward in PG compared with in OCD while considering repetitive gambling and compulsion as addictive behaviors.

Methods/Principal Findings

To elucidate the neural activities specific to the anticipation phase of reward, we performed event-related functional magnetic resonance imaging (fMRI) in young adults with PG and compared them with those in patients with OCD and healthy controls. Fifteen male patients with PG, 13 patients with OCD, and 15 healthy controls, group-matched for age, gender, and IQ, participated in a monetary incentive delay task during fMRI scanning. Neural activation in the ventromedial caudate nucleus during anticipation of both gain and loss decreased in patients with PG compared with that in patients with OCD and healthy controls. Additionally, reduced activation in the anterior insula during anticipation of loss was observed in patients with PG compared with that in patients with OCD which was intermediate between that in OCD and healthy controls (healthy controls < PG < OCD), and a significant positive correlation between activity in the anterior insula and South Oaks Gambling Screen score was found in patients with PG.

Conclusions

Decreased neural activity in the ventromedial caudate nucleus during anticipation may be a specific neurobiological feature for the pathophysiology of PG, distinguishing it from OCD and healthy controls. Correlation of anterior insular activity during loss anticipation with PG symptoms suggests that patients with PG fit the features of OCD associated with harm avoidance as PG symptoms deteriorate. Our findings have identified functional disparities and similarities between patients with PG and OCD related to the neural responses associated with reward anticipation.     

Reward Anticipation in Ventral Striatum and Individual Sensitivity to Reward: A Pilot Study of a Child-Friendly fMRI Task

Reward processing has been implicated in developmental disorders. However, the classic task to probe reward anticipation, the monetary incentive delay task, has an abstract coding of reward and no storyline and may therefore be less appropriate for use with developmental populations. We modified the task to create a version appropriate for use with children. We investigated whether this child-friendly version could elicit ventral striatal activation during reward anticipation in typically developing children and young adolescents (aged 9.5–14.5). In addition, we tested whether our performance-based measure of reward sensitivity was associated with anticipatory activity in ventral striatum. Reward anticipation was related to activity in bilateral ventral striatum. Moreover, we found an association between individual reward sensitivity and activity in ventral striatum. We conclude that this task assesses ventral striatal activity in a child-friendly paradigm. The combination with a performance-based measure of reward sensitivity potentially makes the task a powerful tool for developmental imaging studies of reward processing.     

Accounting for Dynamic Fluctuations across Time when Examining fMRI Test-Retest Reliability: Analysis of a Reward Paradigm in the EMBARC Study

Longitudinal investigation of the neural correlates of reward processing in depression may represent an important step in defining effective biomarkers for antidepressant treatment outcome prediction, but the reliability of reward-related activation is not well understood. Thirty-seven healthy control participants were scanned using fMRI while performing a reward-related guessing task on two occasions, approximately one week apart. Two main contrasts were examined: right ventral striatum (VS) activation fMRI BOLD signal related to signed prediction errors (PE) and reward expectancy (RE). We also examined bilateral visual cortex activation coupled to outcome anticipation. Significant VS PE-related activity was observed at the first testing session, but at the second testing session, VS PE-related activation was significantly reduced. Conversely, significant VS RE-related activity was observed at time 2 but not time 1. Increases in VS RE-related activity from time 1 to time 2 were significantly associated with decreases in VS PE-related activity from time 1 to time 2 across participants. Intraclass correlations (ICCs) in VS were very low. By contrast, visual cortex activation had much larger ICCs, particularly in individuals with high quality data. Dynamic changes in brain activation are widely predicted, and failure to account for these changes could lead to inaccurate evaluations of the reliability of functional MRI signals. Conventional measures of reliability cannot distinguish between changes specified by algorithmic models of neural function and noisy signal. Here, we provide evidence for the former possibility: reward-related VS activations follow the pattern predicted by temporal difference models of reward learning but have low ICCs.     

Functional imaging of neural responses to expectancy and experience of monetary gains and losses

Neural responses accompanying anticipation and experience of monetary gains and losses were monitored by functional magnetic resonance imaging. Trials comprised an initial "prospect" (expectancy) phase, when a set of three monetary amounts was displayed, and a subsequent "outcome" phase, when one of these amounts was awarded. Hemodynamic responses in the sublenticular extended amygdala (SLEA) and orbital gyrus tracked the expected values of the prospects, and responses to the highest value set of outcomes increased monotonically with monetary value in the nucleus accumbens, SLEA, and hypothalamus. Responses to prospects and outcomes were generally, but not always, seen in the same regions. The overlap of the observed activations with those seen previously in response to tactile stimuli, gustatory stimuli, and euphoria-inducing drugs is consistent with a contribution of common circuitry to the processing of diverse rewards.     

Amphetamine Sensitization Alters Reward Processing in the Human Striatum and Amygdala

Dysregulation of mesolimbic dopamine transmission is implicated in a number of psychiatric illnesses characterised by disruption of reward processing and goal-directed behaviour, including schizophrenia, drug addiction and impulse control disorders associated with chronic use of dopamine agonists. Amphetamine sensitization (AS) has been proposed to model the development of this aberrant dopamine signalling and the subsequent dysregulation of incentive motivational processes. However, in humans the effects of AS on the dopamine-sensitive neural circuitry associated with reward processing remains unclear. Here we describe the effects of acute amphetamine administration, following a sensitising dosage regime, on blood oxygen level dependent (BOLD) signal in dopaminoceptive brain regions during a rewarded gambling task performed by healthy volunteers. Using a randomised, double-blind, parallel-groups design, we found clear evidence for sensitization to the subjective effects of the drug, while rewarded reaction times were unchanged. Repeated amphetamine exposure was associated with reduced dorsal striatal BOLD signal during decision making, but enhanced ventromedial caudate activity during reward anticipation. The amygdala BOLD response to reward outcomes was blunted following repeated amphetamine exposure. Positive correlations between subjective sensitization and changes in anticipation- and outcome-related BOLD signal were seen for the caudate nucleus and amygdala, respectively. These data show for the first time in humans that AS changes the functional impact of acute stimulant exposure on the processing of reward-related information within dopaminoceptive regions. Our findings accord with pathophysiological models which implicate aberrant dopaminergic modulation of striatal and amygdala activity in psychosis and drug-related compulsive disorders.     

Brain creatine kinase activity in an animal model of mania

There is evidence pointing to dysfunction at the mitochondrial level as an important target for the understanding of the pathophysiology of bipolar disorder (BD). We assessed creatine kinase (CK) activity in rats submitted to an animal model of mania which included the use of lithium and valproate. In the acute treatment, amphetamine (AMPH) or saline was administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the maintenance treatment, rats were pretreated with lithium, valproate or saline, and between day 8 and 14, AMPH or saline were administered. In both experiments, locomotor activity was assessed by open-field test and CK activity was evaluated in hippocampus, striatum, cerebellum, whole cortex and prefrontal cortex. Our results showed that mood stabilizers reversed AMPH-induced behavioral effects. Moreover, AMPH (acute treatment) inhibited CK activity in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex, and administration of lithium or valproate did not reverse the enzyme inhibition. In the maintenance treatment, AMPH decreased CK activity in saline-pretreated rats in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex. AMPH administration in lithium- or valproate-pretreated animals decreased CK activity in hippocampus, striatum and cortex. Our results showed that AMPH inhibited CK activity and that mood stabilizers were not able to reverse and/or prevent the enzyme inhibition. These findings reinforce the hypothesis that mitochondrial dysfunction plays an important role in the pathophysiology of BD.     

PLAC1 expression increases during trophoblast differentiation: evidence for regulatory interactions with the fibroblast growth factor-7 (FGF-7) axis

PLAC1 is a recently described, trophoblast-specific gene that localizes to a region of the X-chromosome important in placental development. Immunohistochemical analysis demonstrated that PLAC1 polypeptide localizes to the differentiated syncytiotrophoblast throughout gestation (8-41 weeks) as well as a small population of villous cytotrophoblasts. Consistent with these observations, quantitative RT-PCR demonstrated that PLAC1 mRNA increases more than 300-fold during cytotrophoblast differentiation in culture to form syncytiotrophoblasts. Agents known to be relevant to trophoblast differentiation were then tested for the ability to influence PLAC1 expression. Fibroblast growth factor-7 (FGF-7), also known as keratinocyte growth factor (KGF), stimulated PLAC1 mRNA expression approximately two-fold in the BeWo(b30) trophoblast cell line. FGF-7 stimulation was significantly inhibited by PD-98059 and wortmannin suggesting mediation via MAP kinase and PI-3 kinase-dependent signaling pathways. Interestingly, epidermal growth factor (EGF) treatment of trophoblasts had no effect on PLAC1 expression alone, but potentiated the effect of FGF-7, suggesting the presence of a regulatory interaction of the two growth factors. FGF-7 and its receptor, FGFR-2b, exhibited spatial overlap with PLAC1 suggesting these regulatory interactions are physiologically relevant during gestation. These data demonstrate PLAC1 expression is upregulated during trophoblast differentiation, localizing primarily to the differentiated syncytiotrophoblast. Furthermore PLAC1 expression is specifically regulated by peptide growth factors relevant to trophoblast differentiation.     

Effects of amphetamine on schedule-induced polydipsia

A series of experiments examined the effects of amphetamine (AMPH) at various doses administration for different length of time on a schedule-induced polydipsia (SIP) and possible associations with behavioral activation. Two stages of a two-week AMPH treatment were introduced with interposed interval of two months. In terms of behavioral activation, AMPH induced a robust depression across stages but with less potency in the second one. As for the SIP performance, the effects manifested qualitative difference in the two stages. For the first stage, there were no differential effects of AMPH on stereotypy intensity during the facultative phase of the inter-rewarding interval. However, AMPH reduced the high frequency of licks in the adjunctive (schedule-induced) phase and increased the low frequency of nose pokes in the terminal (schedule-dependent) phase. In the second stage, AMPH had no effect on the frequency of licking whereas the efficiency of licking and the frequency of nose pokes were reduced. These results were interpreted to support the current viewpoint that the behavior of SIP displaying is relevant to the function of central dopaminergic systems. The results were further discussed in the considerations of behavioral competition, stress coping strategy, and also the impact of AMPH at different time.     

Rat Strain Differences in Responses of Plasma Prolactin and PRL mRNA Expression After Acute Amphetamine Treatment or Restraint Stress

1. The aim of this study was to compare the effects of acute amphetamine (AMPH) treatment and restraint stress on plasma level of prolactin (PRL) and PRL mRNA expression in the adenohypophysis in Sprague–Dawley and Lewis male rats, the latter known to have a deficient hypothalamo–pituitary-adrenal (HPA) axis.2. Both restraint stress and AMPH treatment (i.p. in a dose of 8 mg/kg of b.w.) were applied 15 or 30 min before termination of the experiment. Plasma PRL and corticosterone (CORT) were determined by radioimmunoassay. PRL mRNA expression was estimated by a dot-blot hybridization.3. Restraint stress and AMPH treatment induced a significant increase in theCORT plasma level, as an indicator of stress response. Compared to Sprague–Dawley rats, the magnitude of CORT increase after both stimuli was significantly lower in Lewis rats.4. Although restraint stress significantly increased the PRL plasma levels in both rat strains, AMPH treatment reduced the PRL levels in both rat strains. However, the changes of PRL plasma levels had another pattern in Lewis rats than in Sprague–Dawley rats. Control plasma PRL levels were significantly higher in Lewis rats, and in this rat strain AMPH treatment for 30 min increased the PRL levels as compared to the values obtained after AMPH treatment for 15 min.5. Expression of PRL mRNA in adenohypophysis by restraint stress and AMPH treatment had a similar pattern. After a 15-min lasting restraint stress, the expression of PRL mRNA was decreased insignificantly in both rat strains. AMPH treatment induced in Sprague–Dawley rats a significant decrease of PRL mRNA after a 15-min interval while after 30 min there was a significant increase. However, in Lewis rats AMPH failed to significantly change PRL mRNA.6. The results from the present study indicate that the mechanisms mediatingthe effects of acute restraint stress and acute AMPH treatment differ in PRL response in Sprague–Dawley and Lewis male rat strains. Differences in the observed responses in Lewis rats could be related to the deficient activity of HPA axis in this rat strain.     

Amphetamine and Methamphetamine Differentially Affect Dopamine Transporters in Vitro and in Vivo

The psychostimulants d-amphetamine (AMPH) and methamphetamine (METH) release excess dopamine (DA) into the synaptic clefts of dopaminergic neurons. Abnormal DA release is thought to occur by reverse transport through the DA transporter (DAT), and it is believed to underlie the severe behavioral effects of these drugs. Here we compare structurally similar AMPH and METH on DAT function in a heterologous expression system and in an animal model. In the in vitro expression system, DAT-mediated whole-cell currents were greater for METH stimulation than for AMPH. At the same voltage and concentration, METH released five times more DA than AMPH and did so at physiological membrane potentials. At maximally effective concentrations, METH released twice as much [Ca²⁺]_i from internal stores compared with AMPH. [Ca²⁺]_i responses to both drugs were independent of membrane voltage but inhibited by DAT antagonists. Intact phosphorylation sites in the N-terminal domain of DAT were required for the AMPH- and METH-induced increase in [Ca²⁺]_i and for the enhanced effects of METH on [Ca²⁺]_i elevation. Calmodulin-dependent protein kinase II and protein kinase C inhibitors alone or in combination also blocked AMPH- or METH-induced Ca²⁺ responses. Finally, in the rat nucleus accumbens, in vivo voltammetry showed that systemic application of METH inhibited DAT-mediated DA clearance more efficiently than AMPH, resulting in excess external DA. Together these data demonstrate that METH has a stronger effect on DAT-mediated cell physiology than AMPH, which may contribute to the euphoric and addictive properties of METH compared with AMPH.The dopamine transporter (DAT)³ is a main target for psychostimulants, such as d-amphetamine (AMPH), methamphetamine (METH), cocaine (COC), and methylphenidate (Ritalin®). DAT is the major clearance mechanism for synaptic dopamine (DA) (1) and thereby regulates the strength and duration of dopaminergic signaling. AMPH and METH are substrates for DAT and competitively inhibit DA uptake (2, 3) and release DA through reverse transport (4–9). AMPH- and METH-induced elevations in extracellular DA result in complex neurochemical changes and profound psychiatric effects (2, 10–16). Despite their structural and pharmacokinetic similarities, a recent National Institute on Drug Abuse report describes METH as a more potent stimulant than AMPH with longer lasting effects at comparable doses (17). Although the route of METH administration and its availability must contribute to the almost four times higher lifetime nonmedical use of METH compared with AMPH (18), there may also be differences in the mechanisms that underlie the actions of these two drugs on the dopamine transporter.Recent studies by Joyce et al. (19) have shown that compared with d-AMPH alone, the combination of d- and l-AMPH in Adderall® significantly prolonged the time course of extracellular DA in vivo. These experiments demonstrate that subtle structural features of AMPH, such as chirality, can affect its action on dopamine transporters. Here we investigate whether METH, a more lipophilic analog of AMPH, affects DAT differently than AMPH, particularly in regard to stimulated DA efflux.METH and AMPH have been reported as equally effective in increasing extracellular DA levels in rodent dorsal striatum (dSTR), nucleus accumbens (NAc) (10, 14, 20), striatal synaptosomes, and DAT-expressing cells in vitro (3, 6). John and Jones (21), however, have recently shown in mouse striatal and substantia nigra slices, that AMPH is a more potent inhibitor of DA uptake than METH. On the other hand, in synaptosomes METH inhibits DA uptake three times more effectively than AMPH (14), and in DAT-expressing COS-7 cells, METH releases DA more potently than AMPH (EC₅₀ = 0.2 μm for METH versus EC₅₀ = 1.7 μm for AMPH) (5). However, these differences do not hold up under all conditions. For example, in a study utilizing C6 cells, the disparity between AMPH and METH was not found (12).The variations in AMPH and METH data extend to animal models. AMPH- and METH-mediated behavior has been reported as similar (22), lower (20), or higher (23) for AMPH compared with METH. Furthermore, although the maximal locomotor activation response was less for METH than for AMPH at a lower dose (2 mg/kg, intraperitoneal), both drugs decreased locomotor activity at a higher dose (4 mg/kg) (20). In contrast, in the presence of a salient stimuli, METH is more potent in increasing the overall magnitude of locomotor activity in rats yet is equipotent with AMPH in the absence of these stimuli (23).The simultaneous regulation of DA uptake and efflux by DAT substrates such as AMPH and METH, as well as the voltage dependence of DAT (24), may confound the interpretation of existing data describing the action of these drugs. Our biophysical approaches allowed us to significantly decrease the contribution of DA uptake and more accurately determine DAT-mediated DA efflux with millisecond time resolution. We have thus exploited time-resolved, whole-cell voltage clamp in combination with in vitro and in vivo microamperometry and Ca²⁺ imaging to compare the impact of METH and AMPH on DAT function and determine the consequence of these interactions on cell physiology.We find that near the resting potential, METH is more effective than AMPH in stimulating DAT to release DA. In addition, at efficacious concentrations METH generates more current, greater DA efflux, and higher Ca²⁺ release from internal stores than AMPH. Both METH-induced or the lesser AMPH-induced increase in intracellular Ca²⁺ are independent of membrane potential. The additional Ca²⁺ response induced by METH requires intact phosphorylation sites in the N-terminal domain of DAT. Finally, our in vivo voltammetry data indicate that METH inhibits clearance of locally applied DA more effectively than AMPH in the rat nucleus accumbens, which plays an important role in reward and addiction, but not in the dorsal striatum, which is involved in a variety of cognitive functions. Taken together these data imply that AMPH and METH have distinguishable effects on DAT that can be shown both at the molecular level and in vivo, and are likely to be implicated in the relative euphoric and addictive properties of these two psychostimulants.     

Placenta specific 8 gene induces epithelial-mesenchymal transition of nasopharyngeal carcinoma cells via the TGF-β/Smad pathway

The present study aimed to investigate the effects and mechanisms of PLAC8 on the epithelial-mesenchymal transition (EMT) of Nasopharyngeal carcinoma (NPC). The expression of PLAC8 in NPC and nasopharyngitis (NPG) tissues from 150 patients was determined using immunohistochemistry. The levels of PLAC8 in five NPC cell lines and nasopharyngeal permanent epithelial cell line were measured using western blotting. We then knocked out or overexpressed PLAC8 in CNE2 cells. Cell proliferation, wound healing, migration, and invasion assays were used to analyze the effects of PLAC8 on the proliferation, migration, and invasion in vivo and vitro. The results showed that the expression of PLAC8 was much higher in NPC tissues than in NPG tissues. The expression of PLAC8 was higher in all the cell lines than in the nasopharyngeal permanent epithelial cells. PLAC8 knockout resulted in significant decreases in cell proliferation, migration, and invasion; associated with lower protein levels of N-cadherin; and increased levels of E-cadherin. Overexpression of PLAC8 had the opposite effect. Furthermore, knockout of PLAC8 inactivated TGF-β/SMAD signaling pathway and suppressed the growth of NPC xenografts. PLAC8 may promote the carcinogenesis and EMT of NPC via the TGF-β/Smad pathway, which suggests that PLAC8 may be a potential biomarker for NPC.     

Amphetamine treatment during early postnatal development transiently restricts somatic growth

AimsRestricted somatic growth during fetal or early postnatal periods has been suggested to serve as a predictive indicator for neuroanatomical changes and behavioral impairments during adulthood. Here, the effects of d-amphetamine sulfate (AMPH) exposure during the brain growth spurt period on this potential indicator were evaluated.Main methodsRats received 0, 5, 15 or 25 mg/kg/day of AMPH via two daily intragastric intubations from PD4-9. Body weight data were collected every other day from PD1 to 21, and then weekly until PD59. On PD9, a subset of animals was terminated 90 min after the last amphetamine treatment and the weights of the cortex, cerebellum, and brainstem were collected. Weights of these brain regions from young adult rats were also assessed on PD68.Key findingsAMPH exposure during early postnatal development limited somatic growth in a dose-related manner, with significantly lower body weights in animals assigned to the AMPH 25 and AMPH 15 groups. However, this was transient in nature, with no significant difference in weight observed after pups were weaned on PD21. Further, no differences in brain weight were observed at either age as a result of AMPH exposure.SignificanceThese findings support the idea that developmental AMPH exposure transiently restricts somatic growth. Moreover, the lack of effect on brain weight shows that AMPH differentially affects somatic and brain growth. The current findings suggest that in addition to the immediate effects on body weight, amphetamine may alter the rate of growth, and increase the risk for weight-related adult diseases.     

Interdependent utilities: how social ranking affects choice behavior

Organization in hierarchical dominance structures is prevalent in animal societies, so a strong preference for higher positions in social ranking is likely to be an important motivation of human social and economic behavior. This preference is also likely to influence the way in which we evaluate our outcome and the outcome of others, and finally the way we choose. In our experiment participants choose among lotteries with different levels of risk, and can observe the choice that others have made. Results show that the relative weight of gains and losses is the opposite in the private and social domain. For private outcomes, experience and anticipation of losses loom larger than gains, whereas in the social domain, gains loom larger than losses, as indexed by subjective emotional evaluations and physiological responses. We propose a theoretical model (interdependent utilities), predicting the implication of this effect for choice behavior. The relatively larger weight assigned to social gains strongly affects choices, inducing complementary behavior: faced with a weaker competitor, participants adopt a more risky and dominant behavior.     

The effect of hormonal condition on dose-dependent amphetamine-stimulated behaviors in the male rat

The effects of varying doses (1.25, 2.5, and 5.0 mg/kg, ip) of D-amphetamine sulfate (AMPH) on eight individual behaviors (Rearing, Grooming, Sniffing, Stationary, Gnawing, Head Bobbing, "Sleeping," and Licking) of Castrate + Oil-treated, Castrate + Testosterone Propionate (TP)-treated, and Intact male rats were examined. For Stationary, Sniffing, and "Sleeping" at 1.25 mg/kg AMPH and Rearing and Sniffing at the 2.5 mg/kg dose a significantly greater duration in the behavioral score was obtained for Castrate + Oil versus Castrate + TP and Intact males. These results indicate the complexity of the AMPH dose-response effects upon measurable behaviors, the alteration in the duration of these effects as a function of the hormonal condition of the male rat, and the importance of examining discrete components of behavior when hormone-amphetamine interactions are examined.     

A single intrategmental amphetamine exposure induces transient behavioral sensitization in the rats

Repeated treatment with psychostimulant drugs induces enduring behavioral sensitization and neuroadaptations which may play an important role in the development of drug addiction. However, different number and time course in drug administration and various lengths of drug withdrawal were employed in the literature, and there were inconsistent findings in the profile of extracellular dopamine level related to behavioral sensitization. Therefore, the effects of the number of drug exposure and the length of drug withdrawal period on the sensitized behavioral response were investigated in this study. Various lengths of amphetamine (AMPH) withdrawal (1, 3 and 5 days) after a single local administration of AMPH to bilateral ventral tegmental area (VTA) were used to observe the locomotor activity response. Besides, different amounts of administration of intra-VTA AMPH were given (1, 2 and 3 times of injection) to monitor the profile of travel distance and stereotypic movements of rats after 7 days of drug withdrawal. An early and short-lived behavioral sensitization to the single intra-VTA AMPH administration was induced. In the repeated treatment group, more drug exposures were associated with escalating and robust levels of travel distance after 7 days of drug withdrawal. The authors speculated that the transient and, a later augmented locomotor activity response might represent respective phases in the development of behavioral sensitization, which in turn contributed to the formation of more lasting behavioral and neuroplastic changes associated with drug addiction.     

The Effect of Positive and Negative Feedback on Risk-Taking across Different Contexts

Preferences for risky choices have often been shown to be unstable and context-dependent. Though people generally avoid gambles with mixed outcomes, a phenomenon often attributed to loss aversion, contextual factors can impact this dramatically. For example, people typically prefer risky options after a financial loss, while generally choosing safer options after a monetary gain. However, it is unclear what exactly contributes to these preference shifts as a function of prior outcomes, as these gain/loss outcomes are usually confounded with participant performance, and therefore it is unclear whether these effects are driven purely by the monetary gains or losses, or rather by success or failure at the actual task. Here, we experimentally separated the effects of monetary gains/losses from performance success/failure prior to a standard risky choice. Participants performed a task in which they experienced contextual effects: 1) monetary gain or loss based directly on performance, 2) monetary gain or loss that was randomly awarded and was, crucially, independent from performance, and 3) success or failure feedback based on performance, but without any monetary incentive. Immediately following these positive/negative contexts, participants were presented with a gain-loss gamble that they had to decide to either play or pass. We found that risk preferences for identical sets of gambles were biased by positive and negative contexts containing monetary gains and losses, but not by contexts containing performance feedback. This data suggests that the observed framing effects are driven by aversion for monetary losses and not simply by the positive or negative valence of the context, or by potential moods resulting from positive or negative contexts. These results highlight the specific context dependence of risk preferences.     

The acute effects of a caffeine-containing supplement on bench press strength and time to running exhaustion

The purpose of the present study was to examine the acute effects of a caffeine-containing supplement (SUPP) on one-repetition maximum (1-RM) bench press strength and time to running exhaustion (TRE) at a velocity that corresponded to 85% of the peak oxygen uptake ([latin capital V with dot above]O2peak). The study used a double-blinded, placebo-controlled, crossover design. Thirty-one men (mean +/- SD age = 23.0 +/- 2.6 years) were randomly assigned to take either the SUPP or placebo (PLAC) first. The SUPP contained 201 mg of caffeine, and the PLAC was microcrystalline cellulose. All subjects were tested for 1-RM bench press strength and TRE at 45 minutes after taking either the SUPP or PLAC. After 1 week of rest, the subjects returned to the laboratory and ingested the opposite substance (SUPP or PLAC) from what was taken during the previous visit. The 1-RM bench press and TRE tests were then performed in the same manner as before. The results indicated that the SUPP had no effect on 1-RM bench press strength or TRE at 85% [latin capital V with dot above]O2peak. It is possible that the acute effects of caffeine are affected by differences in training status and/or the relative intensity of the exercise task. Future studies should examine these issues, in addition to testing the acute effects of various caffeine doses on performance during maximal strength, power, and aerobic activities. These findings do not, however, support the use of caffeine as an ergogenic aid in untrained to moderately trained individuals.     

Involvement of hypothalamic neuropeptide Y in regulating the amphetamine-induced appetite suppression in streptozotocin diabetic rats

BACKGROUND AND AIM: Amphetamine (AMPH) is a well-known anorectic agent. In normal rats, AMPH-induced anorexia has been attributed to its inhibitory action on hypothalamic neuropeptide Y (NPY), an appetite stimulant in the brain. In diabetic rats, however, if this anorectic response of AMPH might still be observed was uncertain. METHODS: Rats (including normal, diabetic and insulin-treated diabetic rats) were given daily with saline or AMPH for 6 days. Changes in food intake, plasma glucose level (PGL) and NPY content of these rats were measured and compared. RESULTS: The AMPH-induced anorectic response was altered in diabetic rats. Although the anorectic effects of AMPH on the first day of dosing were similar between diabetic and control rats, diabetic rats developed tolerance to this anorexia more rapidly than control rats. This alteration was independent of PGL since PGL levels were not changed following AMPH treatment and PGL normalization induced by phlorizin could not restore the level of AMPH anorexia. On the other hand, this alteration was dependent on the action of NPY because NPY contents were decreased following AMPH treatment and the replacement of insulin in diabetic rats could restore both NPY content and AMPH anorexia. CONCLUSION: These results suggested that the elevated hypothalamic NPY content in diabetic rats was involved in modifying the anorectic response of AMPH.