The involvement of dopamine in drug reinforcement is well recognized but its role in drug addiction is much less clear. Imaging studies have shown that the reinforcing effects of drugs of abuse in humans are contingent upon large and fast increases in dopamine that mimic but exceed in the intensity and duration those induced by dopamine cell firing to environmental events. In addition, imaging studies have also documented a role of dopamine in motivation, which appears to be encoded both by fast as well as smooth DA increases. Since dopamine cells fire in response to salient stimuli, the supraphysiological activation by drugs is likely to be experienced as highly salient (driving attention, arousal conditioned learning and motivation) and may also reset the thresholds required for environmental events to activate dopamine cells. Indeed, imaging studies have shown that in drug-addicted subjects, dopamine function is markedly disrupted (decreases in dopamine release and in dopamine D2 receptors in striatum) and this is associated with reduced activity of the orbitofrontal cortex (neuroanatomical region involved with salience attribution and motivation and implicated in compulsive behaviors) and the cingulate gyrus (neuroanatomical region involved with inhibitory control and attention and implicated in impulsivity). However, when addicted subjects are exposed to drug-related stimuli, these hypoactive regions become hyperactive in proportion to the expressed desire for the drug. We postulate that decreased dopamine function in addicted subjects results in decreased sensitivity to nondrug-related stimuli (including natural reinforcers) and disrupts frontal inhibition, both of which contribute to compulsive drug intake and impaired inhibitory control. These findings suggest new strategies for pharmacological and behavioral treatments, which focus on enhancing DA function and restoring brain circuits disrupted by chronic drug use to help motivate the addicted subject in activities that provide alternative sources of reinforcement, counteract conditioned responses, enhance their ability to control their drive to take drugs and interfere with their compulsive administration.

40 years ago, activities in international health were the domain of WHO, governments (based on bilateral agreements), and non-governmental organisations. This has changed. Today, new players (such as the World Bank and, increasingly, the World Trade Organisation) have an influence on international health. As globalisation of trade and markets takes hold, new coalitions and alliances are forming to examine and deal with the direct and indirect consequences on health. This paper examines the changing context of cooperation in international health, and voices concerns about rising potential inequalities in health, both within and between countries. The question of how such changes will affect the actions of organisations working in international health is also addressed.

Associations have been reported of the 7-repeat (7R) allele of the human dopamine receptor D4 (DRD4) gene with both the personality trait of novelty seeking and attention-deficit/ hyperactivity disorder (ADHD). The increased prevalence of the 7R allele in ADHD probands is consistent with the common variant-common disorder hypothesis, which proposes that the high frequency of many complex genetic disorders is related to common DNA variants. Recently, based on the unusual DNA sequence organization and strong linkage disequilibrium surrounding the DRD4 7R allele, we proposed that this allele originated as a rare mutational event, which nevertheless increased to high prevalence in human populations by positive selection. We have now determined, by DNA resequencing of 250 DRD4 alleles obtained from 132 ADHD probands, that most ADHD 7R alleles are of the conserved haplotype found in our previous 600 allele worldwide DNA sample. Interestingly, however, half of the 24 haplotypes uncovered in ADHD probands were novel (not one of the 56 haplotypes found in our prior population studies). Over 10 percent of the ADHD probands had these novel haplotypes, most of which were 7R allele derived. The probability that this high incidence of novel alleles occurred by chance in our ADHD sample is much less than 0.0001. These results suggest that allelic heterogeneity at the DRD4 locus may also contribute to the observed association with ADHD.

Using a subsample of 105 children and their parents (100 mothers, 57 fathers) from the Multimodal Treatment Study of Children with ADHD (the MTA), the value of parents' baseline cognitions as predictors of children's treatment outcome at 14 months was examined. Measures of parents' cognitions about themselves, their ADHD children, and their parenting, as well as a self-report measure of dysfunctional discipline were included. Both mothers' and fathers' self-reported use of dysfunctional discipline predicted worse child treatment outcome. Low self-esteem in mothers, low parenting efficacy in fathers, and fathers' attributions of noncompliance to their ADHD child's insufficient effort and bad mood also were associated with worse child treatment outcome. All of these predictive relations were obtained even after MTA treatment effects had been taken into account. Secondary analyses indicated that mothers had a more external locus of control, lower self-esteem, lower parenting efficacy, and a greater tendency to attribute noncompliance to their ADHD child's bad mood than did fathers.

Although an association exists between illicit drug use and sexually transmitted diseases (STDs) in known high-risk populations such as prostitutes, gay men, and intravenous drug users, little is known with respect to middle-class, heterosexual populations thought to be at less risk. We examined findings related to illicit drug use among young adults with genital herpes from a larger study of young adults' adaptation to chronic disease. In this cross-sectional retrospective study, 70 subjects age 18 to 35 years were interviewed and asked to fill out questionnaires. The sample was predominantly white, heterosexual, employed, and college educated. Responses to open-ended questions related to illicit drug use were coded and compared with findings from two other surveys: a national household survey, Pacific region, metropolitan areas; and a household survey of a San Francisco Bay area county. All but eight subjects (88.6%) reported that they had used an illicit drug at some time in the past. The median number of drugs used was 4; the maximum number was 11. Only six drug-using subjects reported that they had restricted their use to marijuana. Those with genital herpes were more likely to report ever using an illicit drug at some time in the past, and, more specifically, in the past year, than subjects in the two comparison surveys. Such findings suggest that programs screen for illicit drug use as a risk factor in middle-class young adults with genital herpes and other STDs, and for STDs in persons referred for drug abuse treatment.

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