Activation in mesolimbic and visuospatial neural circuits elicited by smoking cues: evidence from functional magnetic resonance imaging.

OBJECTIVE: The authors sought to increase understanding of the brain mechanisms involved in cigarette addiction by identifying neural substrates modulated by visual smoking cues in nicotine-deprived smokers. METHOD: Event-related functional magnetic resonance imaging (fMRI) was used to detect brain activation after exposure to smoking-related images in a group of nicotine-deprived smokers and a nonsmoking comparison group. Subjects viewed a pseudo-random sequence of smoking images, neutral nonsmoking images, and rare targets (photographs of animals). Subjects pressed a button whenever a rare target appeared. RESULTS: In smokers, the fMRI signal was greater after exposure to smoking-related images than after exposure to neutral images in mesolimbic dopamine reward circuits known to be activated by addictive drugs (right posterior amygdala, posterior hippocampus, ventral tegmental area, and medial thalamus) as well as in areas related to visuospatial attention (bilateral prefrontal and parietal cortex and right fusiform gyrus). In nonsmokers, no significant differences in fMRI signal following exposure to smoking-related and neutral images were detected. In most regions studied, both subject groups showed greater activation following presentation of rare target images than after exposure to neutral images. CONCLUSIONS: In nicotine-deprived smokers, both reward and attention circuits were activated by exposure to smoking-related images. Smoking cues are processed like rare targets in that they activate attentional regions. These cues are also processed like addictive drugs in that they activate mesolimbic reward regions.

Addiction and arousal: the hypocretin connection

The hypocretins, also known as orexins, are two neuropeptides now commonly described as critical components to maintain and regulate the stability of arousal. Several lines of evidence have raised the hypothesis that hypocretin-producing neurons are part of the circuitries that mediate the hypothalamic response to acute stress. Intracerebral administration of hypocretin leads to a dose-related reinstatement of drug and food seeking behaviors. Furthermore, stress-induced reinstatement can be blocked with hypocretin receptor 1 antagonism. These results, together with recent data showing that hypocretin is critically involved in cocaine sensitization through the recruitment of NMDA receptors in the ventral tegmental area, strongly suggest that activation of hypocretin neurons play a critical role in the development of the addiction process. The activity of hypocretin neurons may affect addictive behavior by contributing to brain sensitization or by modulating the brain reward system. Hypocretinergic cells, in coordination with brain stress systems may lead to a vulnerable state that facilitates the resumption of drug seeking behavior. Hence, the hypocretinergic system is a new drug target that may be used to prevent relapse of drug seeking

Using selected scenes from Brazilian films to teach about substance use disorders, within medical education

CONTEXT AND OBJECTIVES: Themes like alcohol and drug abuse, relationship difficulties, psychoses, autism and personality dissociation disorders have been widely used in films. Psychiatry and psychiatric conditions in various cultural settings are increasingly taught using films. Many articles on cinema and psychiatry have been published but none have presented any methodology on how to select material. Here, the authors look at the portrayal of abusive use of alcohol and drugs during the Brazilian cinema revival period (1994 to 2008). DESIGN AND SETTING: Qualitative study at two universities in the state of São Paulo. METHODS: Scenes were selected from films available at rental stores and were analyzed using a specifically designed protocol. We assessed how realistic these scenes were and their applicability for teaching. One author selected 70 scenes from 50 films (graded for realism and teaching applicability > 8). These were then rated by another two judges. Rating differences among the three judges were assessed using nonparametric tests (P < 0.001). Scenes with high scores (> 8) were defined as "quality scenes". RESULTS: Thirty-nine scenes from 27 films were identified as "quality scenes". Alcohol, cannabis, cocaine, hallucinogens and inhalants were included in these. Signs and symptoms of intoxication, abusive/harmful use and dependence were shown. CONCLUSIONS: We have produced rich teaching material for discussing psychopathology relating to alcohol and drug use that can be used both at undergraduate and at postgraduate level. Moreover, it could be seen that certain drug use behavioral patterns are deeply rooted in some Brazilian films and groups.

Enriched environment treatment counteracts enhanced addictive and depressive-like behavior induced by prenatal chronic stress

Prenatal stress can cause many long-term behavior changes in offspring, but whether prenatal stress can alter addictive behavior in offspring and postnatal enriched environment treatment (EE) can restore these changes are unknown. We reported here that pr

Brain damage and addictive behavior: a neuropsychological and electroencephalogram investigation with pathologic gamblers.

BACKGROUND Gambling is a form of nonsubstance addiction classified as an impulse control disorder. Pathologic gamblers are considered healthy with respect to their cognitive status. Lesions of the frontolimbic systems, mostly of the right hemisphere, are associated with addictive behavior. Because gamblers are not regarded as "brain-lesioned" and gambling is nontoxic, gambling is a model to test whether addicted "healthy" people are relatively impaired in frontolimbic neuropsychological functions. METHODS Twenty-one nonsubstance dependent gamblers and nineteen healthy subjects underwent a behavioral neurologic interview centered on incidence, origin, and symptoms of possible brain damage, a neuropsychological examination, and an electroencephalogram. RESULTS Seventeen gamblers (81%) had a positive medical history for brain damage (mainly traumatic head injury, pre- or perinatal complications). The gamblers, compared with the controls, were significantly more impaired in concentration, memory, and executive functions, and evidenced a higher prevalence of non-right-handedness (43%) and, non-left-hemisphere language dominance (52%). Electroencephalogram (EEG) revealed dysfunctional activity in 65% of the gamblers, compared with 26% of controls. CONCLUSIONS This study shows that the "healthy" gamblers are indeed brain-damaged. Compared with a matched control population, pathologic gamblers evidenced more brain injuries, more fronto-temporo-limbic neuropsychological dysfunctions and more EEG abnormalities. The authors thus conjecture that addictive gambling may be a consequence of brain damage, especially of the frontolimbic systems, a finding that may well have medicolegal consequences.

Optimal second best taxation of addictive goods in dynamic general equilibrium: a revenue raising perspective

In this paper we derive conditions under which optimal tax rates for addictive goods exceed tax rates for non-addictive consumption goods within a rational addiction framework where exogenous government spending cannot be financed with lump sum taxes. We reexamine classic results on optimal commodity taxation and find a rich set of new findings. Two dynamic effects exist. First, households anticipating higher future addictive tax rates reduce current addictive consumption, so they will be less addicted when the tax rate increases. Therefore, addictive tax revenue falls prior to the tax increase. Surprisingly, the optimal tax rate on addictive goods is generally decreasing in the strength of tolerance, since strong tolerance strengthens this tax anticipation effect. Second, high current tax rates on addictive goods make households less addicted in the future, affecting all future tax revenues in a way which depends on how elasticities are changing over time. Classic results on uniform commodity taxation emerge as special cases when elasticities are constant and the addiction function is homogeneous of degree one. Finally, we also study features of addictive goods such as complementarity to leisure that, while not directly related to the definition of addiction, are nonetheless properties many addictive goods display.

Psychiatric severity and behavior change in alcoholism

Individuals who are diagnosed with a chronic mental illness and an alcohol use disorder comprise a high risk population that challenges the mental health care system. Effective treatment for the dually diagnosed, who are characterized by heterogeneity in their psychiatric diagnoses, their substance use patterns, and their current degree of dysfunction, presents a challenge. Several integrated treatment models have been developed that attempt to concurrently treat patients' psychiatric and substance abuse problems. At this point in the development of these "dual diagnosis" programs, treatment planning is hindered by a lack of knowledge about the relation of psychiatric severity to the process of recovery from alcohol abuse and dependence.^ The present study sought to advance the field's understanding of the relation between psychiatric severity and the process of behavior change through an examination of the relation between dimensions of psychiatric severity and Prochaska and DiClemente's Transtheoretical Model (TTM) constructs. The TTM, which focuses on identifying the processes of change that appear to underlie the modification of addictive behaviors, provides a way of conceptualizing and measuring specific elements relevant to the desired behavior change. Knowledge of the relation between these constructs and psychiatric severity will enable treatment planners to develop dual diagnosis programs which target clients' needs with a much higher level of specificity.^ One hundred-thirty two alcohol dependent patients in a dual diagnosis treatment program were assessed on psychiatric severity (defined as number of symptoms and level of distress resulting from symptoms) and the Transtheoretical Model constructs. The constructs include stages and processes of change for alcohol use, alcohol decisional balance, and alcohol abstinence self-efficacy. Results indicate that the TTM variable of "temptation to drink" is most strongly related to psychiatric severity: the more psychiatric distress a person is experiencing, the more he or she is tempted to drink. The "cons" of drinking were also related to psychiatric severity, indicating that participants who were experiencing more psychiatric distress also endorsed as important a higher number of the negative aspects of drinking.^ Additional aims of this investigation were to determine whether participants' scores on the Transtheoretical Model variables were associated with their: (a) severity of drinking, defined as frequency, quantity and consequences of use, (b) previous psychiatric and substance abuse treatment episodes, and (c) functional impairment. Associations were found among these variables and each of the key constructs of the Transtheoretical Model. Each association is explored in detail and implications for treatment programming are discussed. ^

Dopamine receptor D4 polymorphism predicts the effect of L-DOPA on gambling behavior

BACKGROUND There is ample evidence that a subgroup of Parkinson's disease patients who are treated with dopaminergic drugs develop certain behavioral addictions such as pathological gambling. The fact that only a subgroup of these patients develops pathological gambling suggests an interaction between dopaminergic drug treatment and individual susceptibility factors. These are potentially of genetic origin, since research in healthy subjects suggests that vulnerability for pathological gambling may be linked to variation in the dopamine receptor D4 (DRD4) gene. Using a pharmacogenetic approach, we investigated how variation in this gene modulates the impact of dopaminergic stimulation on gambling behavior in healthy subjects. METHODS We administered 300 mg of L-dihydroxyphenylalanine (L-DOPA) or placebo to 200 healthy male subjects who were all genotyped for their DRD4 polymorphism. Subjects played a gambling task 60 minutes after L-DOPA administration. RESULTS Without considering genetic information, L-DOPA administration did not lead to an increase in gambling propensity compared with placebo. As expected, however, an individual's DRD4 polymorphism accounted for variation in gambling behavior after the administration of L-DOPA. Subjects who carry at least one copy of the 7-repeat allele showed an increased gambling propensity after dopaminergic stimulation. CONCLUSIONS These findings demonstrate that genetic variation in the DRD4 gene determines an individual's gambling behavior in response to a dopaminergic drug challenge. They may have implications for the treatment of Parkinson's disease patients by offering a genotype approach for determining individual susceptibilities for pathological gambling and may also afford insights into the vulnerability mechanisms underlying addictive behavior.

Cocaine-predictive stimulus induces drug-seeking behavior and neural activation in limbic brain regions after multiple months of abstinence: Reversal by D1 antagonists

The conditioning of cocaine's subjective actions with environmental stimuli may be a critical factor in long-lasting relapse risk associated with cocaine addiction. To study the significance of learning factors in persistent addictive behavior as well as the neurobiological basis of this phenomenon, rats were trained to associate discriminative stimuli (SD) with the availability of i.v. cocaine vs. nonrewarding saline solution, and then placed on extinction conditions during which the i.v. solutions and SDs were withheld. The effects of reexposure to the SD on the recovery of responding at the previously cocaine-paired lever and on Fos protein expression then were determined in two groups. One group was tested immediately after extinction, whereas rats in the second group were confined to their home cages for an additional 4 months before testing. In both groups, the cocaine SD, but not the non-reward SD, elicited strong recovery of responding and increased Fos immunoreactivity in the basolateral amygdala and medial prefrontal cortex (areas Cg1/Cg3). The response reinstatement and Fos expression induced by the cocaine SD were both reversed by selective dopamine D1 receptor antagonists. The undiminished efficacy of the cocaine SD to elicit drug-seeking behavior after 4 months of abstinence parallels the long-lasting nature of conditioned cue reactivity and cue-induced cocaine craving in humans, and confirms a significant role of learning factors in the long-lasting addictive potential of cocaine. Moreover, the results implicate D1-dependent neural mechanisms within the medial prefrontal cortex and basolateral amygdala as substrates for cocaine-seeking behavior elicited by cocaine-predictive environmental stimuli.

The Behavior of Hydroxyl Units of Synthetic Goethite and its Dehydroxylated Product Hematite

The behavior of the hydroxyl units of synthetic goethite and its dehydroxylated product hematite was characterized using a combination of Fourier transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) during the thermal transformation over a temperature range of 180-270 degrees C. Hematite was detected at temperatures above 200 degrees C by XRD while goethite was not observed above 230 degrees C. Five intense OH vibrations at 3212-3194, 1687-1674, 1643-1640, 888-884 and 800-798 cm(-1), and a H2O vibration at 3450-3445 cm(-1) were observed for goethite. The intensity of hydroxyl stretching and bending vibrations decreased with the extent of dehydroxylation of goethite. Infrared absorption bands clearly show the phase transformation between goethite and hematite: in particular. the migration of excess hydroxyl units from goethite to hematite. Two bands at 536-533 and 454-452 cm(-1) are the low wavenumber vibrations of Fe-O in the hematite structure. Band component analysis data of FTIR spectra support the fact that the hydroxyl units mainly affect the a plane in goethite and the equivalent c plane in hematite.

Let's Dance: A Language for Service Behavior Modeling

In Service-Oriented Architectures (SOAs), software systems are decomposed into independent units, namely services, that interact with one another through message exchanges. To promote reuse and evolvability, these interactions are explicitly described right from the early phases of the development lifecycle. Up to now, emphasis has been placed on capturing structural aspects of service interactions. Gradually though, the description of behavioral dependencies between service interactions is gaining increasing attention as a means to push forward the SOA vision. This paper deals with the description of these behavioral dependencies during the analysis and design phases. The paper outlines a set of requirements that a language for modeling service interactions at this level should fulfill, and proposes a language whose design is driven by these requirements.

Multiple-choice versus short-response items: Differences in omit behavior

The overall rate of omission of items for 28,331 17 year old Australian students on a high stakes test of achievement in the common elements or cognitive skills of the senior school curriculum is reported for a subtest in multiple choice format and a subtest in short response format. For the former, the omit rates were minuscule and there was no significant difference by gender or by type of school attended. For the latter, where an item can be 'worth' up to five times that of a single multiple choice item, the omit rates were between 10 and 20 times that for multiple choice and the difference between male and female omit rate was significant as was the difference between students from government and non-government schools. For both formats, females from single sex schools omitted significantly fewer items than did females from co-educational schools. Some possible explanations of omit behaviour are alluded to.