男性酒依赖患者食欲素A与急性期戒断反应的相关性

目的探讨男性酒依赖患者血浆食欲素A(orexin-A,OXA)浓度与急性期酒精戒断反应、心理渴求之间的关系。方法纳入60例男性酒依赖患者和60名健康成年男性。收集一般人口学资料,检测血浆OXA浓度,以及总胆固醇、肌酸激酶、谷丙转氨酶、谷草转氨酶、血糖及血钾水平,使用修订版临床酒精戒断症状评估量表中文版(clinic institute alcohol withdrawal syndrome scale,CIWA-Ar)及视觉模拟量表(visual analogues scale,VAS)评估患者酒精戒断反应严重程度和心理渴求程度;患者组接受戒酒治疗14 d后,再次检测OXA及血生化指标,以及评估CIWA-Ar及VAS。结果入组时患者组血浆OXA、总胆固醇、肌酸激酶、谷丙转氨酶、谷草转氨酶及血糖水平高于对照组(均P<0.05),血钾浓度低于对照组(P<0.05)。在入组时患者组中轻度戒断反应者血浆OXA水平低于中度或重度戒断反应者(均P<0.05)。患者组治疗前后血浆OXA浓度、CIWA-Ar评分、VAS得分存在统计学差异(均P<0.05)。患者入组时血浆OXA的水平与CIWA-Ar评分(r=0.34,P<0.01)和VAS评分(r=0.47,P<0.01)均具有统计学相关性。结论在急性酒精戒断期男性酒依赖患者血浆OXA水平可能与戒断反应、渴求有关。     

Impulsivity and adolescent substance use: rashly dismissed as "all-bad"?

The initial use of illicit drugs and alcohol typically occurs during adolescence. Individual differences in impulsivity and related constructs are consistently identified as key factors in the initiation and later problematic use of substances. Consequently, impulsivity is generally regarded as a negative trait; one that conveys only risk. However, what is often overlooked in addiction science is the positive role facets of trait impulsivity can play in everyday life and adaptive functioning. The following review aims to summarize recent advances in the psychobiology of impulsivity, including current perspectives on how it can convey risk for substance misuse. The review will also consider the importance of adolescence as a phase of life characterized by substantial neurodevelopment and natural increases in impulsivity. Uniquely, the review aims to reframe thinking on adolescent impulsivity to include the positive with the negative, and discuss how such thinking can benefit efforts for early intervention and future research.     

Increased self-reported reward responsiveness predicts better response to cognitive behavioral therapy for youth with anxiety

Few consistent predictors of differential cognitive behavioral therapy (CBT) outcome for anxious youth have been identified, although emerging literature points to youth reward responsiveness as a potential predictor. In a sample of youth ages 7–17 with a primary anxiety disorder (N = 136; M_age = 12.18 years, SD_age = 3.12; 70 females; Caucasian n = 108, Black n = 12, Asian n = 4, Hispanic n = 5, other n = 7), the current study examined whether youth reward responsiveness assessed via the Behavioral Inhibition and Behavioral Activation System Scales for children, reward responsiveness subscale, predicted post-treatment (a) anxiety symptom severity, (b) depressive symptom severity, (c) functioning, (d) responder status and (e) number of homework/exposure tasks completed following 16-weeks of CBT, controlling for pre-treatment age, sex, anxiety/depressive symptom severity, and functioning. Moderation analyses examined whether relationships differed by age. Increased reward responsiveness was associated with lower anxiety and depressive symptom severity, higher functioning, and increased likelihood of being a responder, but not homework or exposure completion. Moderation analyses showed that younger, but not older, youth who were more reward responsive completed more exposures. Findings indicate that increased reward responsiveness is a predictor of better CBT outcomes for anxious youth, particularly functional outcomes, and that reward responsiveness may play a different role in exposure completion across development.     

Brief report: Personality correlates of susceptibility to peer influence in adolescence

Adolescents show a heightened susceptibility to peer influence compared to adults. Individual differences in this susceptibility exist, yet there has been little effort to link these with broader personality processes. Reward sensitivity and impulsive behaviour are also heightened in adolescence and could affect the tendency to be influenced by peers. This study examined associations between self-reported resistance to peer influence, facets of reward sensitivity and impulsivity, and subjective social status in a sample of 269 British sixth form students (mean age 16.79). Multiple regression analyses showed that negative and positive urgency were significantly negatively associated with resistance to peer influence. The relationship between negative urgency and resistance was moderated by subjective social status, such that individuals reporting low status showed a stronger negative relationship. Results suggest that a susceptibility to peer influence is linked with a tendency to act impulsively when in heightened emotional states. Adolescents high in negative urgency who feel lower in their social hierarchy may be particularly vulnerable.     

A non-reward attractor theory of depression

A non-reward attractor theory of depression is proposed based on the operation of the lateral orbitofrontal cortex and supracallosal cingulate cortex. The orbitofrontal cortex contains error neurons that respond to non-reward for many seconds in an attractor state that maintains a memory of the non-reward. The human lateral orbitofrontal cortex is activated by non-reward during reward reversal, and by a signal to stop a response that is now incorrect. Damage to the human orbitofrontal cortex impairs reward reversal learning. Not receiving reward can produce depression. The theory proposed is that in depression, this lateral orbitofrontal cortex non-reward system is more easily triggered, and maintains its attractor-related firing for longer. This triggers negative cognitive states, which in turn have positive feedback top-down effects on the orbitofrontal cortex non-reward system. Treatments for depression, including ketamine, may act in part by quashing this attractor. The mania of bipolar disorder is hypothesized to be associated with oversensitivity and overactivity in the reciprocally related reward system in the medial orbitofrontal cortex and pregenual cingulate cortex.     

Altered processing of rewarding and aversive basic taste stimuli in symptomatic women with anorexia nervosa and bulimia nervosa: An fMRI study

Functional magnetic resonance imaging (fMRI) studies have displayed a dysregulation in the way in which the brain processes pleasant taste stimuli in patients with anorexia nervosa (AN) and bulimia nervosa (BN). However, exactly how the brain processes disgusting basic taste stimuli has never been investigated, even though disgust plays a role in food intake modulation and AN and BN patients exhibit high disgust sensitivity. Therefore, we investigated the activation of brain areas following the administration of pleasant and aversive basic taste stimuli in symptomatic AN and BN patients compared to healthy subjects. Twenty underweight AN women, 20 symptomatic BN women and 20 healthy women underwent fMRI while tasting 0.292 M sucrose solution (sweet taste), 0.5 mM quinine hydrochloride solution (bitter taste) and water as a reference taste. In symptomatic AN and BN patients the pleasant sweet stimulus induced a higher activation in several brain areas than that induced by the aversive bitter taste. The opposite occurred in healthy controls. Moreover, compared to healthy controls, AN patients showed a decreased response to the bitter stimulus in the right amygdala and left anterior cingulate cortex, while BN patients showed a decreased response to the bitter stimulus in the right amygdala and left insula. These results show an altered processing of rewarding and aversive taste stimuli in ED patients, which may be relevant for understanding the pathophysiology of AN and BN.     

Varenicline attenuates nicotine-enhanced brain-stimulation reward by activation of α4β2 nicotinic receptors in rats

Varenicline, a partial α4β2 and full α7 nicotinic receptor agonist, has been shown to inhibit nicotine self-administration and nicotine-induced increases in extracellular dopamine in the nucleus accumbens. In the present study, we investigated whether varenicline inhibits nicotine-enhanced electrical brain-stimulation reward (BSR), and if so, which receptor subtypes are involved. Systemic administration of nicotine (0.25-1.0 mg/kg, i.p.) or varenicline (0.03-3 mg/kg, i.p.) produced biphasic effects, with low doses producing enhancement (e.g., decreased BSR threshold), and high doses inhibiting BSR. Pretreatment with low dose (0.03-1.0 mg/kg) varenicline dose-dependently attenuated nicotine (0.25 or 0.5 mg/kg)-enhanced BSR. The BSR-enhancing effect produced by varenicline was blocked by mecamylamine (a high affinity nicotinic receptor antagonist) or dihydro-β-erythroidine (a relatively selective nicotinic α4-containing receptor antagonist), but not methyllycaconitine (a selective α7 receptor antagonist), suggesting an effect mediated by activation of α4β2 receptors. This suggestion is supported by findings that the α4β2 receptor agonist SIB-1765F produced a dose-dependent enhancement of BSR, while pretreatment with SIB-1765F attenuated nicotine (0.5 mg/kg)-enhanced BSR. In contrast, the selective α7 receptor agonist ARR-17779, altered neither BSR itself nor nicotine-enhanced BSR, at any dose tested. These findings suggest that: 1) varenicline inhibits nicotine-enhanced BSR, supporting its use as a smoking cessation aid; and 2) varenicline-enhanced BSR by itself and varenicline's anti-nicotine effects are mediated by activation of α4β2, but not α7, receptors.     

Altered reward functions in patients on atypical antipsychotic medication in line with the revised dopamine hypothesis of schizophrenia

Objective  To study the mesolimbic dopamine system during expectation and receipt or omission of rewards in partially remitted patients with schizophrenia treated with the atypical antipsychotic olanzapine. Methods  We studied 16 patients with a current episode of schizophrenia, all treated with the atypical drug olanzapine, and 16 healthy subjects using functional magnetic resonance imaging. Subjects performed a delayed incentive paradigm with monetary rewards. Results  During reward expectation, both, patients with schizophrenia and healthy control subjects, showed activation of the ventral striatum and midbrain in the vicinity of the ventral tegmental area. Significant categorical group differences emerged in the anterior cingulate cortex with only healthy controls showing increasing activation with increasing reward. In the patients, activation of this region was inversely correlated with positive symptoms. During outcome, both, patients with schizophrenia and healthy controls, showed activation of the ventral striatum and the mesial prefrontal cortex. Significant categorical group differences emerged in the right ventrolateral prefrontal cortex for the salience contrast with healthy controls showing a U-shaped activation curve, i.e., higher activation for either omission or receipt of reward compared to no reward. Conclusions  Our findings partially support the current concept of dopaminergic dysfunction in schizophrenia, suggesting a rather hyperactive mesolimbic dopamine system and reduced prefrontal activation, at least in partially remitted patients treated with atypical antipsychotics.     

Hedonic sensitivity in adolescent and adult rats: Taste reactivity and voluntary sucrose consumption

Adolescents have been hypothesized to exhibit an age-related partial anhedonia that may lead them to seek out natural and drug rewards to compensate for this attenuated hedonic sensitivity. In the present series of experiments, taste reactivity (TR) and 2 bottle choice tests were used to assess hedonic reactions to sucrose.In Exp 1, total positive taste responses to 10% sucrose solution were significantly higher in adolescent than adult rats during the infusion period. In Exp 2, adolescent animals exhibited a concentration-effect shift that was consistent with a greater hedonic sensitivity compared to adults. Conversely, adolescents exhibited fewer negative responses to quinine. Using a shortened infusion period, adolescents in Exp 3 exhibited a trend for greater positive TR than adults in response to 10 and 34% sucrose. Consistent with the TR results of Exp 1-3, adolescents consumed significantly more sucrose solution (ml/kg) than adults, although no significant age difference in sucrose preference rates emerged.The results of the current series of experiments do not support the hypothesis that adolescents exhibit an age-related, partial anhedonia, with adolescent animals, under a number of test circumstances showing greater positive taste reactivity and reduced negative responding.     

Conditioned place preference induced by social play behavior: Parametrics, extinction, reinstatement and disruption by methylphenidate

In this study, we investigated behavioral factors underlying conditioned place preference (CPP) induced by social interaction in adolescent rats. We found that the magnitude of socially-induced CPP depended on the social motivation of the animals and on the amount of training. After extinction, socially-induced CPP could be reinstated by a single reconditioning session. Treatment with methylphenidate, which disrupts social play behavior in adolescent rats, but not social exploratory behavior, prevented the development of socially-induced CPP. Interestingly, methylphenidate by itself induced CPP. These data demonstrate that: 1. social interaction is rewarding in adolescent rats; 2. appetitive and mnemonic factors influence the development of socially-induced CPP; 3. comparable to drug-induced CPP, socially-induced CPP can be extinguished and reinstated; 4. social play is likely to be the most rewarding aspect of social interaction in adolescent rats; 5. social context influences the subjective effects of methylphenidate.