Showing papers on "Addiction published in 2002"
TL;DR: Recent neurophysiological studies reveal that neurons in certain brain structures carry specific signals about past and future rewards, and the optimal use of rewards in voluntary behavior would benefit from interactions between the signals.
2,478 citations
TL;DR: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed, and results imply that addiction connotes cortically regulated cognitive and emotional processes, which result in the overvaluing of drug reinforcers, the undervalued of alternative rein forcers, and deficits in inhibitory control for drug responses.
Abstract: OBJECTIVE: Studies of the neurobiological processes underlying drug addiction primarily have focused on limbic subcortical structures. Here the authors evaluated the role of frontal cortical structures in drug addiction. METHOD: An integrated model of drug addiction that encompasses intoxication, bingeing, withdrawal, and craving is proposed. This model and findings from neuroimaging studies on the behavioral, cognitive, and emotional processes that are at the core of drug addiction were used to analyze the involvement of frontal structures in drug addiction. RESULTS: The orbitofrontal cortex and the anterior cingulate gyrus, which are regions neuroanatomically connected with limbic structures, are the frontal cortical areas most frequently implicated in drug addiction. They are activated in addicted subjects during intoxication, craving, and bingeing, and they are deactivated during withdrawal. These regions are also involved in higher-order cognitive and motivational functions, such as the ability to tr...
2,415 citations
TL;DR: An associative learning hypothesis is proposed according to which stimuli contingent upon drug reward acquire powerful incentive properties after a relatively limited number of predictive associations with the drug and become particularly resistant to extinction.
927 citations
TL;DR: The reinforcing (rewarding) effects of psychomotor stimulants (cocaine and amphetamine) depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens, perhaps especially the shell subregion.
Abstract: The reinforcing (rewarding) effects of psychomotor stimulants (cocaine and amphetamine) depend on the mesocorticolimbic dopamine system innervating the nucleus accumbens ([Wise, 1981][1]; for review, see[Koob, 1992][2]), perhaps especially the shell subregion ([Bassareo and Di Chiara, 1997][3]).
685 citations
TL;DR: Current animal research regarding the most salient threats to the development and maintenance of extinction is reviewed, and several major procedures for increasing the efficacy of cue-exposure addiction treatment are suggested.
Abstract: Aims To evaluate the efficacy of cue-exposure addiction treatment and review modern animal learning research to generate recommendations for substantially enhancing the effectiveness of this treatment. Design Meta-analysis of cue-exposure addiction treatment outcome studies (N = 9), review of animal extinction research and theory, and evaluation of whether major principles from this literature are addressed adequately in cue-exposure treatments. Findings The meta-analytical review showed that there is no consistent evidence for the efficacy of cue-exposure treatment as currently implemented. Moreover, procedures derived from the animal learning literature that should maximize the potential of extinction training are rarely used in cue-exposure treatments. Conclusions Given what is known from animal extinction theory and research about extinguishing learned behavior, it is not surprising that cue-exposure treatments so often fail. This paper reviews current animal research regarding the most salient threats to the development and maintenance of extinction, and suggests several major procedures for increasing the efficacy of cue-exposure addiction treatment.
631 citations
TL;DR: PET imaging data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction.
Abstract: Disruption of the dopaminergic system has been implicated in the etiology of many pathological conditions, including drug addiction. Here we used positron emission tomography (PET) imaging to study brain dopaminergic function in individually housed and in socially housed cynomolgus macaques (n = 20). Whereas the monkeys did not differ during individual housing, social housing increased the amount or availability of dopamine D2 receptors in dominant monkeys and produced no change in subordinate monkeys. These neurobiological changes had an important behavioral influence as demonstrated by the finding that cocaine functioned as a reinforcer in subordinate but not dominant monkeys. These data demonstrate that alterations in an organism's environment can produce profound biological changes that have important behavioral associations, including vulnerability to cocaine addiction.
609 citations
TL;DR: Preclinical and clinical studies indicate that ovarian hormones, particularly estrogen, play a role in producing sex differences in drug abuse, and it is necessary to provide information on how to design more effective drug abuse treatment programs and resources that are sex specific.
Abstract: The recent focus on drug abuse in women has brought attention to numerous differences between women and men. In this review, we discuss both preclinical and clinical findings of sex differences in drug abuse as well as mechanisms that may underlie these differences. Recent evidence suggests that the progression to dependence and abuse may differ between women and men; thus, different prevention and treatment strategies may be required. Similar sex differences in drug sensitivity and self-administration have been reported in laboratory animal studies. Females appear to be more vulnerable than males to the reinforcing effects of psychostimulants, opiates, and nicotine during many phases of the addiction process (e.g. acquisition, maintenance, dysregulation-escalation, relapse). Male and female animals differ in their behavioral, neurological, and pharmacological responses to drugs. Although the role of sex in the mechanisms of drug action remains unclear, preclinical and clinical studies indicate that ovarian hormones, particularly estrogen, play a role in producing sex differences in drug abuse. Future research is necessary to provide information on how to design more effective drug abuse treatment programs and resources that are sex specific.
548 citations
TL;DR: It is shown that environmental stimuli regulate CRE-mediated transcription within the nucleus accumbens shell, and that changes in CREB activity within this brain area subsequently alter gating between emotional stimuli and their behavioral responses.
Abstract: The transcription factor cAMP response element (CRE)-binding protein (CREB) has been shown to regulate neural plasticity. Drugs of abuse activate CREB in the nucleus accumbens, an important part of the brain's reward pathways, and local manipulations of CREB activity have been shown to affect cocaine reward, suggesting an active role of CREB in adaptive processes that follow exposure to drugs of abuse. Using CRE-LacZ reporter mice, we show that not only rewarding stimuli such as morphine, but also aversive stimuli such as stress, activate CRE-mediated transcription in the nucleus accumbens shell. Using viral-mediated gene transfer to locally alter the activity of CREB, we show that this manipulation affects morphine reward, as well as the preference for sucrose, a more natural reward. We then show that local changes in CREB activity induce a more general syndrome, by altering reactions to anxiogenic, aversive, and nociceptive stimuli as well. Increased CREB activity in the nucleus accumbens shell decreases an animal's responses to each of these stimuli, whereas decreased CREB activity induces an opposite phenotype. These results show that environmental stimuli regulate CRE-mediated transcription within the nucleus accumbens shell, and that changes in CREB activity within this brain area subsequently alter gating between emotional stimuli and their behavioral responses. This control appears to be independent of the intrinsic appetitive or aversive value of the stimulus. The potential relevance of these data to addiction and mood disorders is discussed.
508 citations
TL;DR: It is postulate that dopamine contributes to addiction by disrupting the frontal cortical circuits that regulate motivation, drive, and self-control and by memory circuits that increase the motivational salience of the drug and drug-associated stimuli.
500 citations
TL;DR: It is probable that by promoting physical fitness, increased physical performance, lessening body mass and promoting a more favourable body shape and structure, exercise will provide more positive social feedback and recognition from peer groups, and this will subsequently lead to improvement in an individual's self-image.
Abstract: Background: Although there are a vast array of studies which have demonstrated the psychological and physical health benefits of regular aerobic exercise for adults, few studies have focussed on children and adolescents. The current study examined associations between the extent of participation in endurance sport, and self-report data on self-image, physical and psychological health and overall lifestyle in a large representative sample of German high-school students. Method: Almost 1000 German adolescents (aged 14–18 years) were administered a comprehensive series of questionnaires aimed at assessing anxiety-depression, trait addiction, smoking and drinking behaviour, physical ill-health reports, and self-perception of self-image, parental acceptance and educational attainment. Results: Regular practice of endurance exercise was related to a more favourable self-image. There was a strong association between participation in sports and the type of personality that tends to be resistant to drug and alcohol addiction. Physical exercise was further significantly related to scores for physical and psychological well-being. Adolescents who engaged regularly in physical activity were characterised by lower anxiety-depression scores, and displayed much less social behavioural inhibition than their less active counterparts. Conclusion: It is likely that discussion of recreational or exercise involvement may provide a useful point of entry for facilitating dialogue among adolescents about concerns relating to body image and self-esteem. In terms of psychotherapeutic applications, physical activity has many additional rewards for adolescents. It is probable that by promoting physical fitness, increased physical performance, lessening body mass and promoting a more favourable body shape and structure, exercise will provide more positive social feedback and recognition from peer groups, and this will subsequently lead to improvement in an individual's self-image.
445 citations
TL;DR: Examination of the nAChR subtypes expressed within the reward centers has identified potential roles for these receptors in normal physiology, as well as the effects of nicotine exposure.
Abstract: The tragic health effects of nicotine addiction highlight the importance of investigating the cellular mechanisms of this complex behavioral phenomenon. The chain of cause and effect of nicotine addiction starts with the interaction of this tobacco alkaloid with nicotinic acetylcholine receptors (nAChRs). This interaction leads to activation of reward centers in the CNS, including the mesoaccumbens DA system, which ultimately leads to behavioral reinforcement and addiction. Recent findings from a number of laboratories have provided new insights into the biologic processes that contribute to nicotine self-administration. Examination of the nAChR subtypes expressed within the reward centers has identified potential roles for these receptors in normal physiology, as well as the effects of nicotine exposure. The high nicotine sensitivity of some nAChR subtypes leads to rapid activation followed in many cases by rapid desensitization. Assessing the relative importance of these molecular phenomena in the behavioral effects of nicotine presents an exciting challenge for future research efforts.
TL;DR: Data obtained from animal studies show that glucocorticoid hormones have a facilitatory role on behavioural responses to psychostimulant drugs such as locomotor activity, self‐administration and relapse, and suggest that an increase in glucoc Corticoids, through an action on mesolimbic dopamine neurons, could increase vulnerability to drug abuse.
Abstract: In this review we summarize data obtained from animal studies showing that glucocorticoid hormones have a facilitatory role on behavioural responses to psychostimulant drugs such as locomotor activity, self-administration and relapse. These behavioural effects of glucocorticoids involve an action on the meso-accumbens dopamine system, one of the major systems mediating the addictive properties of drugs of abuse. The effects of glucocorticoids in the nucleus accumbens are site-specific; these hormones modify dopamine transmission in only the shell of this nucleus without modifying it in the core. Studies with corticosteroid receptor antagonists suggest that the dopaminergic effects of these hormones depend mostly on glucocorticoid, not on mineralocorticoid receptors. These data suggest that an increase in glucocorticoid hormones, through an action on mesolimbic dopamine neurons, could increase vulnerability to drug abuse. We also discuss the implications of this finding with respect to the physiological role of glucocorticoids. It is proposed that an increase in glucocorticoids, by activating the reward pathway, could counteract the aversive effects of stress. During chronic stress, repeated increases in glucocorticoids and dopamine would result in sensitization of the reward system. This sensitized state, which can persist after the end of the stress, would render the subject more responsive to drugs of abuse and consequently more vulnerable to the development of addiction.
TL;DR: Drug addiction can be understood as a pathological subversion of normal brain learning and memory processes strengthened by the motivational impact of drug-associated stimuli, leading to the establishment of compulsive drug-seeking habits.
TL;DR: Despite the effectiveness of medications, they must be used in conjunction with appropriate psychosocial treatments, because they act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects.
Abstract: Opioid tolerance, dependence, and addiction are all manifestations of brain changes resulting from chronic opioid abuse. The opioid abuser’s struggle for recovery is in great part a struggle to overcome the effects of these changes. Medications such as methadone, LAAM, buprenorphine, and naltrexone act on the same brain structures and processes as addictive opioids, but with protective or normalizing effects. Despite the effectiveness of medications, they must be used in conjunction with appropriate psychosocial treatments.
TL;DR: The current approved and implemented pharmacotherapeutic approaches to the treatment of addiction are summarized, and the most promising areas for future drug development are highlighted from the perspective of the laboratory and NIDA Research Center.
Abstract: Addiction to drugs, such as heroin, cocaine and alcohol, exacts great human and financial costs on society, but the development of pharmacotherapies for addiction has been largely neglected by the pharmaceutical industry. With advances in our understanding of the underlying biology of addictions now opening the door for the development of novel pharmacotherapies, it could be time for a reassessment of involvement in this increasingly important therapeutic area. Here, we summarize the current approved and implemented pharmacotherapeutic approaches to the treatment of addiction, and then highlight the most promising areas for future drug development from the perspective of our laboratory and our National Institutes of Health (NIH) National Institute on Drug Abuse (NIDA) Research Center.
TL;DR: A better understanding of the molecular and cellular adaptations that occur in these neural circuits may lead to novel interventions to improve memory and combat addiction in humans.
TL;DR: It is shown in rats that repeated withdrawals from prolonged cocaine self-administration produces a persistent decrease in brain reward function that is highly correlated with escalation of cocaine intake and that reduces the hedonic impact of cocaine.
Abstract: A paradoxical aspect of the transition to drug addiction is that drug users spend progressively more time and effort to obtain drug hedonic effects that continually decrease with repeated experience. According to the hedonic allostasis hypothesis, increased craving for and tolerance to the hedonic effects of drugs result from the same chronic alteration in the regulation of brain reward function (allostasis). Here we show in rats that repeated withdrawals from prolonged cocaine self-administration produces a persistent decrease in brain reward function that is highly correlated with escalation of cocaine intake and that reduces the hedonic impact of cocaine.
TL;DR: It is shown that during drug intoxication increases in striatal DA are associated with the drug's reinforcing effects only if the DA changes occur rapidly, corroborate the relevance of drug-induced DA increases and of pharmacokinetics in the rewarding effects of drugs in humans.
Abstract: The involvement of dopamine (DA) in drug reinforcement is well established, but much less in known about its contribution to addiction. We have used positron emission tomography to investigate in humans the role of DA in drug reinforcement, addiction and drug vulnerability. We have shown that during drug intoxication increases in striatal DA are associated with the drug's reinforcing effects only if the DA changes occur rapidly. These results corroborate the relevance of drug-induced DA increases and of pharmacokinetics in the rewarding effects of drugs in humans. During withdrawal, we have shown significant reductions in DA D(2) receptors and in DA release in drug abusers, which is likely to result in decreased sensitivity to non-drug-related reinforcing stimuli. The DA D(2) reductions were associated with decreased activity in the orbitofrontal cortex, which we postulate is one of the mechanisms underlying compulsive drug administration in the addict. In fact, during craving the orbitofrontal cortex becomes hyperactive in proportion to the desire for the drug. In non-drug-abusing subjects striatal DA D(2) receptors levels predicted the reinforcing responses to stimulant drugs, providing evidence that striatal DA D(2) receptors modulate reinforcing responses to stimulants in humans and may contribute to the predisposition for drug self-administration.
TL;DR: Alcohol research has focused on the identification of brain mechanisms that support the reinforcing actions of alcohol and the progression of changes in neural function induced by chronic ethanol consumption that lead to the development of dependence.
Abstract: Addictive behavior associated with alcoholism is characterized by compulsive preoccupation with obtaining alcohol, loss of control over consumption, and development of tolerance and dependence, as well as impaired social and occupational functioning. Like other addictive disorders, alcoholism is characterized by chronic vulnerability to relapse after cessation of drinking. To understand the factors that compel some individuals to drink excessively, alcohol research has focused on the identification of brain mechanisms that support the reinforcing actions of alcohol and the progression of changes in neural function induced by chronic ethanol consumption that lead to the development of dependence. More recently, increasing attention has been directed toward the understanding of neurobiological and environmental factors in susceptibility to relapse.
TL;DR: It is concluded that Brown's conception of behavioural addiction can be applied toComputer-related behaviour, although the relationship of milder facets of addiction, which are also merely indicative of high engagement, to computer-related addictions is non-unique.
Abstract: Evidence supporting the application of Brown's (1991, 1993) conception of behavioural addiction to computing behaviour is presented. Questionnaire items tapping Brown's addiction criteria were factor-analysed along with others, including computer apathy-engagement and computer anxiety-comfort items of Charlton and Birkett (1995). Items relating to some of Brown's criteria (tolerance, euphoria, and cognitive salience) were found to be complex, an Addiction factor loading upon them but an Engagement factor loading more highly. Items tapping other criteria (conflict, withdrawal, behavioural salience, and relapse and reinstatement) were shown to be factor pure, with only the addiction factor loading highly upon them. It is concluded that Brown's conception of behavioural addiction can be applied to computer-related behaviour, although the relationship of milder facets of addiction, which are also merely indicative of high engagement, to computer-related addictions is non-unique. It is also concluded that classifying individuals as exhibiting pathological computer use using checklists based upon adaptations of DSM criteria for pathological gambling is likely to overestimate the number of people addicted to computing activities.
TL;DR: The authors address the schism between applied-theoretical perspectives and research evidence by suggesting alternative conceptual models of the relationship between neurocognitive impairment and addiction treatment outcome.
Abstract: Between 50% and 80% of individuals with alcohol use disorders experience mild to severe neurocognitive impairment. There is a strong clinical rationale that neurocognitive impairment is an important source of individual difference affecting many aspects of addiction treatment, but empirical tests of the direct influence of impairment on treatment outcome have yielded weak and inconsistent results. The authors address the schism between applied-theoretical perspectives and research evidence by suggesting alternative conceptual models of the relationship between neurocognitive impairment and addiction treatment outcome. Methods to promote neurocognitive recovery and ways in which addiction treatments may be modified to improve psychosocial adaptation are suggested. Specific suggestions for future research that may help clarify the complex relations between neurocognitive impairment and addiction treatment are outlined.
TL;DR: Stress reduction, either alone or in combination with pharmacotherapies targeting the HPA axis may prove beneficial in reducing cravings and promoting abstinence in individuals seeking treatment for cocaine addiction.
Abstract: The hypothalamo-pituitary-adrenal (HPA) axis is involved in all aspects of cocaine self-administration. Corticosterone seems to be crucial for the acquisition of drug use since self-administration does not occur unless this stress hormone is increased above a critical reward threshold. Increasing circulating levels of corticosterone also augments sensitivity to low doses of cocaine, possibly from a sensitization-associated phenomenon involving dopamine, suggesting that exposure to stress can increase individual vulnerability to cocaine. Drugs affecting the synthesis and/or secretion of corticosterone decrease ongoing, low-dose cocaine self-administration. When higher doses falling on the descending limb of the cocaine dose-response curve are self-administered, plasma corticosterone can still reach this reward threshold even when synthesis is inhibited and drug intake is not affected. Corticotropin-releasing hormone (CRH) seems to play a more prominent role in the maintenance of cocaine self-administration and may even be involved in the incentive motivation for the drug. Corticosterone and CRH are also critical for the stress- and cue-induced reinstatement of extinguished cocaine-seeking behavior. Therefore, cocaine self-administration may represent an attempt to seek out specific sensations, with the internal state produced being very similar to that perceived by individuals who engage in risky, thrill-seeking behavior. During abstinence, exposure to stressors or cocaine-associated cues can stimulate the HPA axis to remind the individual about the effects of cocaine, thus producing craving and promoting relapse. Stress reduction, either alone or in combination with pharmacotherapies targeting the HPA axis may prove beneficial in reducing cravings and promoting abstinence in individuals seeking treatment for cocaine addiction.
TL;DR: An important role for D3 receptors in mediating the addictive properties of cocaine is suggested and blockade of dopamine D3receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction.
Abstract: The dopamine D 3 receptor is preferentially localized to the mesocorticolimbic dopaminergic system and has been hypothesized to play a role in cocaine addiction. To study the involvement of the D 3 receptor in brain mechanisms and behaviors commonly assumed to be involved in the addicting properties of cocaine, the potent and selective D 3 receptor antagonist trans-N -[4-[2-(6-cyano-1,2,3,4-tetrahydroisoquinolin-2-yl)ethyl] cyclohexyl]-4-quinolininecarboxamide (SB-277011-A) was administered to laboratory rats, and the following measures were assessed: (1) cocaine-enhanced electrical brain-stimulation reward, (2) cocaine-induced conditioned place preference, and (3) cocaine-triggered reinstatement of cocaine seeking behavior. Systemic injections of SB-277011-A were found to (1) block enhancement of electrical brain stimulation reward by cocaine, (2) dose-dependently attenuate cocaine-induced conditioned place preference, and (3) dose-dependently attenuate cocaine-triggered reinstatement of cocaine seeking behavior. Thus, D 3 receptor blockade attenuates both the rewarding effects of cocaine and cocaine-induced drug-seeking behavior. These data suggest an important role for D 3 receptors in mediating the addictive properties of cocaine and suggest that blockade of dopamine D 3 receptors may constitute a new and useful target for prospective pharmacotherapies for cocaine addiction.
TL;DR: Evidence is reviewed that the ability of drugs of abuse to elevate levels of the GluR1 subunit of AMPA glutamate receptors in the ventral tegmental area (VTA) of the midbrain is crucial for the development of sensitization.
TL;DR: The recent development of a model of adolescent nicotine administration in rats that recapitulates the plasma levels of nicotine found in smokers is described, indicating that adolescence represents a unique period of vulnerability for nicotine-induced misprogramming of brain cell development and synaptic function.
TL;DR: Evidence for common substrates for food and for drug rewards in animals and in humans is brought together to advance fundamental knowledge of motivational processes and to promote the development of better treatments for drug addiction and for eating disorders.
TL;DR: Dysfunction of central dopaminergic neurotransmission has been implicated in the pathogenesis of schizophrenia as well as drug and alcohol dependence and its dysfunction in different neuropsychiatric diseases.
TL;DR: The use of multiple techniques by many laboratories provides optimism that the field is advancing toward elucidating the basic mechanisms of nicotine dependence, and studies of mice lacking nicotinic acetylcholine receptor subunits or expressing supersensitive forms of these subunits have begun to tie together the molecular, neurochemical, and behavioral effects of nicotine.
Abstract: Nicotine addiction is a complex behavioral phenomenon comprising effects on several neural systems. Recent studies have expanded initial observations that the actions of nicotine on dopaminergic systems increase dopaminergic activity and release, leading to nicotine-induced reinforcement. Indeed, the actions of nicotine on many systems, including brainstem cholinergic, GABAergic, noradrenergic, and serotonergic nuclei, may help to mediate nicotine effects related to addiction. Furthermore, studies of mice lacking nicotinic acetylcholine receptor subunits or expressing supersensitive forms of these subunits have begun to tie together the molecular, neurochemical, and behavioral effects of nicotine. The use of multiple techniques by many laboratories provides optimism that the field is advancing toward elucidating the basic mechanisms of nicotine dependence.
TL;DR: Evidence that these potential therapeutic effects may be mediated by modulation of mesolimbic dopamine neurons is reviewed, suggesting that this line of research may also improve the understanding of the neurochemical mechanisms underlying the drug dependence process.
TL;DR: The prediction that patients with anorexia nervosa (AN) would be more anhedonic than those with bulimia nervosa(BN) was tested-a factor that could contribute to their respective avoidance and approach relationship to food.