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What goads cigarette smokers to smoke? Neural adaptation and the mirror neuron system.

One model of addiction suggests that neural circuits in the frontal cortex adapt to drug use and become sensitized leading to excessive attribution of incentive salience to drug-associated cues. The present study examined changes associated with cigarette use in the frontal mirror neuron system (MNS) of the human brain, as reflected in mu rhythm responsiveness. Mirror neurons in premotor cortex exhibit visuomotor properties that allow them to respond to self-movement as well as the observation of movement. This is a potential neural substrate for imitation learning and social cognition, factors that may be important in determining who does and does not develop addictive behaviors. EEG mu rhythm suppression is hypothesized to reflect MNS activity and thus provide a non-invasive method for studying this relationship. Our results show that while nonsmokers exhibit normal mu suppression to observed and self-generated actions, smokers exhibit normal suppression only to self-movement but not to the observation of movement, particularly actions involving addiction-related cues. Non-abstinent and abstinent smokers (those abstaining for approximately 12 h) did not differ significantly in their responses to the observation of movement, i.e., both exhibited atypical patterns of mu rhythm reactivity compared to nonsmokers. These data support the hypothesis that cigarette use produces short- and longer term adaptations in the MNS. Such adaptations may inappropriately bias attention toward motivationally salient, addiction-related cues leading to more impulsive and addiction-related behaviors.

Adolescent↗

Organizational impact of workaholism: suggestions for researching the negative outcomes of excessive work.

Excessive work can be viewed as an addictive behavior, and, as such, it will have a negative impact on the setting in which it occurs, as well as on the individual. This change in perspective is needed to address dysfunctional behavior patterns that interfere with organizational operations. Similarities with other addictions include identity issues, rigid thinking, withdrawal, progressive involvement, and denial. These factors influence decision making and goals of the workaholic. They also interfere with effectiveness by distorting interpersonal relations. Suggestions for further research build on established organizational topics that coincide with characteristics of an addictive pattern.

Behavior, Addictive↗

A validation study of a pain classification system for advanced cancer patients using content experts: the Edmonton Classification System for Cancer Pain.

The purpose of this study was to gather construct validity evidence for a pain classification system for advanced cancer patients using content experts. Two expert panels, representing regional (Panel A, n = 18) and national/international (Panel B, n = 52) palliative medicine and pain specialists, were purposefully selected to participate in a modified Delphi survey technique, to evaluate an existing pain classification system, the Revised Edmonton Staging System (rESS). Each panel participated in two survey rounds, with response rates of 67% (Panel A, Round 1), 39% (Panel A, Round 2), 56% (Panel B, Round 1) and 64% (Panel B, Round 2). The rESS consists of five features: mechanism of pain, incidental pain, psychological distress, addictive behavior and cognitive function. Most participants either agreed or strongly agreed with including the five existing rESS features in a pain classification system, ranging from 67% (Panel A, cognitive function) to 100% (Panel B, mechanism of pain). Most participants suggested keeping the current definitions for these features, with some revisions. Based on participant feedback, definitions for incidental pain, psychological distress, addictive behavior and cognitive function were revised, including the development of guidelines for use. To reflect its intended use as a classification system, the name of the instrument was changed to the Edmonton Classification System for Cancer Pain (ECS-CP).

Humans↗

Relapse as a nonlinear dynamic system: application to patients with alcohol use disorders.

Understanding the relapse process is one of the most important issues in addictive behaviors research. To date, most studies have taken a linear approach toward predicting relapse based on risk factors. Nonlinear dynamical systems theory can be used to describe processes that are not adequately modeled using a linear approach. In particular, the authors propose that catastrophe theory, a subset of nonlinear dynamical systems theory, can be used to describe the relapse process in addictive behaviors. Two small prospective studies using 6-month follow-ups of patients with alcohol use disorders (inpatient, n = 51; outpatient, n = 43) illustrate how cusp catastrophe theory may be used to predict relapse. Results from these preliminary studies indicate that a cusp catastrophe model has more predictive utility than traditional linear models.

Adult↗

A neurobiological basis for substance abuse comorbidity in schizophrenia.

It is commonly held that substance use comorbidity in schizophrenia represents self-medication, an attempt by patients to alleviate adverse positive and negative symptoms, cognitive impairment, or medication side effects. However, recent advances suggest that increased vulnerability to addictive behavior may reflect the impact of the neuropathology of schizophrenia on the neural circuitry mediating drug reward and reinforcement. We hypothesize that abnormalities in the hippocampal formation and frontal cortex facilitate the positive reinforcing effects of drug reward and reduce inhibitory control over drug-seeking behavior. In this model, disturbances in drug reward are mediated, in part, by dysregulated neural integration of dopamine and glutamate signaling in the nucleus accumbens resulting form frontal cortical and hippocampal dysfunction. Altered integration of these signals would produce neural and motivational changes similar to long-term substance abuse but without the necessity of prior drug exposure. Thus, schizophrenic patients may have a predilection for addictive behavior as a primary disease symptom in parallel to, and in many, cases independent from, their other symptoms.

Animals↗

Medico-legal rounds: Medico-legal issues and breaches of "standards of medical care" in opioid tapering for alleged opioid addiction.

OBJECTIVES: The objectives of this medico-legal case report are the following: 1) To present an example of a medico-legal problem that developed as a result of reports of alleged opioid addiction that resulted in a decision to taper a chronic pain patient (CPP) from opioids; 2) To present both the plaintiff's and defendant's expert witness opinions as to if and how the care of that patient fell below the "standard of medical care"; and 3) Based on these opinions, to develop some recommendations on how, in the future, pain medicine physicians and other physicians should proceed in similar circumstances in order to avoid allegations of breach of "standard of medical care." DESIGN: Case Report. SETTING: Regional Hospital Pain Clinic. PATIENT: CPP Interventions. Opioid tapering because of aberrant drug-related behaviors (addictive behaviors). RESULTS: During the tapering process, the CPP committed suicide. This had medico-legal consequences. Expert witnesses could not rule out the possibility of pseudoaddiction in this CPP. CONCLUSION: Further research into the concept of pseudoaddiction is required.

Journal Article↗

Differential effects of donepezil on methamphetamine and cocaine dependencies.

Donepezil, a choline esterase inhibitor, has been widely used as a medicine for Alzheimer's disease. Recently, a study showed that donepezil inhibited addictive behaviors induced by cocaine, including cocaine-conditioned place preference (CPP) and locomotor sensitization to cocaine. In the present study, we investigated the effects of donepezil on methamphetamine (METH)-induced behavioral changes in mice. In counterbalanced CPP tests, the intraperitoneal (i.p.) administration of 3 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit METH CPP, whereas pretreatment with 3 mg/kg donepezil abolished the CPP for cocaine (10 mg/kg, i.p.). Similarly, in locomotor sensitization experiments, i.p. administration of 1 mg/kg donepezil prior to 2 mg/kg METH i.p. failed to inhibit locomotor sensitivity to METH, whereas pretreatment with 1 mg/kg donepezil significantly inhibited locomotor sensitivity to cocaine (10 mg/kg, i.p.). These results suggest that donepezil may be a useful tool for treating cocaine dependence but not for treating METH dependence. The differences in the donepezil effects on addictive behaviors induced by METH and cocaine might be due to differences in the involvement of acetylcholine in the mechanisms of METH and cocaine dependencies.

Amphetamine-Related Disorders↗

Misuse of prescribed controlled substances defined by urinalysis.

The use of controlled substances to treat pain is associated with the need to monitor carefully patients for signs of addictive behaviors that may lead to the misuse or abuse of medications. At the West Virginia Pain Treatment Center in Morgantown, a narcotic protocol is employed which consists of a narcotic contract, consent, psychological evaluation, and random urinalysis to ensure the safe and proper use of controlled substances. This study reports the findings of a retrospective study of 186 patients at the center from Jan. 1, 2001 to Dec. 31, 2001, which revealed that there were 355 infractions of the narcotic contract. Products containing hydrocodone were found to be most frequently misused (20.3%), followed by oxycodone products (19.7%). Patients prescribed controlled substances should be repeatedly evaluated for medication misuse and the presence of addictive behaviors.

Female↗

Human delta-opioid receptor gene and susceptibility to heroin and alcohol dependence.

In the present study, we tested the hypothesis that addictive behavior may be influenced by genetic variation in the human delta-opioid receptor gene. We investigated the contribution of a silent T to C change in the coding region to the development of heroin and alcohol dependence using large case-control and family-based association samples. Presence of the C allele was previously reported to significantly increase the risk for heroin dependence. In the present study, however, we did not find statistically significant differences between patients and controls nor did we find preferential transmission of the C allele from parents to affected offspring. Our results, therefore, do not support an association between genetic variation of the delta-opioid receptor and addictive behavior in man.

Adult↗

Hallucinatory and rewarding effect of salvinorin A in zebrafish: kappa-opioid and CB1-cannabinoid receptor involvement.

RATIONALE: The hallucinatory effect and potential abuse of salvinorin A, the major ingredient of Salvia divinorum, has not been documented in animals. OBJECTIVE: The effects of salvinorin A on the zebrafish (Danio rerio) model, through its swimming behavior and conditioned place preference (CPP) task, was studied. MATERIALS AND METHODS: Swimming activity was determined in a squared observational chamber after an i.m. treatment of salvinorin A (0.1-10 microg/kg). For the CPP test, zebrafish were given salvinorin A (0.2 and 1 microg/kg) or vehicle and evaluated in a two-compartment chamber. RESULTS: Salvinorin A (0.1 and 0.2 microg/kg) induced accelerated swimming behavior in comparison with vehicle, whereas a "trance-like" effect, at doses as 5 and 10 microg/kg, was obtained. Pretreatment with the kappa-opioid antagonist, nor-binaltorphimine (nor-BNI; 10 mg/kg) and the cannabinoid type 1 (CB(1)) antagonist, rimonabant (1 mg/kg), blocked salvinorin A-induced both stimulating and depressive effects obtained at a dose of 0.2 and 10 microg/kg, respectively. In the CPP test, salvinorin A (0.2 and 0.5 microg/kg) produced an increase in the time spent in the drug-associated compartment. A dose of 1 microg/kg produced no effect, whereas a dose of 80 microg/kg induced aversion. Pretreatment with nor-BNI or rimonabant fully reversed the reinforcing properties of salvinorin A (0.5 microg/kg). CONCLUSIONS: Taken together, these results indicate that salvinorin A, as is sometimes reported in humans, exhibits rewarding effects, independently from its motor activity, suggesting the usefulness of the zebrafish model to study addictive behavior. These effects appear mediated by activation of both kappa-opioid and cannabinoid CB(1) receptors.

Animals↗

Voluntary wheel running modulates glutamate receptor subunit gene expression and stress hormone release in Lewis rats.

Lewis rats that are known to be addiction-prone, develop compulsive running if they have access to running wheels. The present experiments were aimed 1) to evaluate the activation of stress systems following chronic and acute voluntary wheel running in Lewis rats by measurement of hormone release and gene expression of neuropeptides related to hypothalamic-pituitary-adrenocortical (HPA) axis activity and 2) to test the hypothesis that wheel running as a combined model of addictive behavior and stress exposure is associated with modulation of ionotropic glutamate receptor subunits in the ventral tegmental area. Voluntary running for three weeks but not for one night resulted in a rise in plasma corticosterone and adrenocorticotropic hormone (ACTH) levels (p<0.05) compared to those in control rats. Principal component analysis revealed the relation between POMC gene expression in the intermediate pituitary and running rate. Acute exposure of animals to voluntary wheel running induced a significant decrease in alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor GluR1 subunit mRNA levels (p<0.01), while repeated voluntary physical activity increased levels of GluR1 mRNA in the ventral tegmentum (p<0.05). Neither acute nor chronic wheel running influenced N-methyl-D-aspartate (NMDA) receptor subunit NR1 mRNA levels in the ventral tegmental area. Thus, the present study revealed changes in AMPA receptor subunit gene expression in a reward-related brain structure as well as an activation of HPA axis in response to compulsive wheel running in Lewis rats. It may be suggested that hormones of HPA axis and glutamate receptors belong to the factors that substantiate higher vulnerability to addictive behavior.

Adrenocorticotropic Hormone↗

Cocaine enhances NMDA receptor-mediated currents in ventral tegmental area cells via dopamine D5 receptor-dependent redistribution of NMDA receptors.

Cocaine-induced plasticity of glutamatergic synaptic transmission in the ventral tegmental area (VTA) plays an important role in brain adaptations that promote addictive behaviors. However, the mechanisms responsible for triggering these synaptic changes are unknown. Here, we examined the effects of acute cocaine application on glutamatergic synaptic transmission in rat midbrain slices. Cocaine caused a delayed increase in NMDA receptor (NMDAR)-mediated synaptic currents in putative VTA dopamine (DA) cells. This effect was mimicked by a specific DA reuptake inhibitor and by a DA D1/D5 receptor agonist. The effect of cocaine was blocked by a DA D1/D5 receptor antagonist as well as by inhibitors of the cAMP/cAMP-dependent protein kinase A (PKA) pathway. Furthermore, biochemical analysis showed an increase in the immunoreactivity of the NMDAR subunits NR1 and NR2B and their redistribution to the synaptic membranes in VTA neurons. Accordingly, NMDAR-mediated EPSC decay time kinetics were significantly slower after cocaine, suggesting an increased number of NR2B-containing NMDARs. Finally, pharmacological analysis indicates that NR2B subunits might be incorporated in triheteromeric NR1/NR2A/NR2B complexes rather than in "pure" NR1/NR2B NMDA receptors. Together, our data suggest that acute cocaine increases NMDAR function in the VTA via activation of the cAMP/PKA pathway mediated by a DA D5-like receptor, leading to the insertion of NR2B-containing NMDARs in the membrane. These results provide a potential mechanism by which acute cocaine promotes synaptic plasticity of VTA neurons, which could ultimately lead to the development of addictive behaviors.

Animals↗

Restrained eaters are rapidly habituating sensation seekers.

Several authors have pointed to similarities between eating disorders and addictive behaviors. In earlier studies, addicts were found to score high on the Sensation Seeking Scale (SSS) and to habituate rapidly to neutral stimuli. In this study, we found experimental support for an addiction model of eating disorders: restrained eaters also scored significantly higher on the Sensation Seeking Scale and also habituated significantly quicker to a series of neutral stimuli than unrestrained eaters. No clear evidence was found for the hypothesis that restrained eaters score lower on measurements of anxiety. It is hypothesized that rapid habituation promotes sensation seeking, which may be manifested in excessive consumption of either drugs or food. Restraint may be a strategy to prevent negative consequences of sensation seeking and excessive consumption. The model is related to earlier experimental findings.

Adult↗

Narcotics addiction treatment: behavioral methods concurrent with methadone maintenance.

Methadone maintenance patients were assigned among four treatment cells involving contingency management, emotionally-based behavior therapy, a combination of these, or a control condition receiving counseling but no behavioral treatment. With 60 patients who remained in treatment at least 6 months, treatment outcomes were compared using objective measures: hours employed, urinalysis results, and counseling participation. No significant differences were found between modalities. Case studies suggested that under appropriate conditions, contingency management might reduce illicit drug use. It is suggested that focused experimental studies may be more productive than broad clinical outcome evaluations.

Adult↗