Journal of addiction research & therapy最新文献

Kappa opioid receptor (KOR) agonists are potentially valuable as therapeutics for the treatment of psychostimulant reward as they suppress dopamine signaling in reward circuitry to repress drug seeking behavior. However, KOR agonists are also associated with sedation and cognitive dysfunction. The extent to which learning and memory disruption or hypolocomotion underlie KOR agonists' role in counteracting the rewarding effects of psychostimulants is of interest. C57BL/6J mice were pretreated with vehicle (saline, 0.9%), the KOR agonist (trans)-3,4-dichloro-N-methyl-N-[2-(1- pyrrolidinyl)-cyclohexyl] benzeneacetamide (U50,488), or the peripherally-restricted agonist D-Phe-D-Phe-D-lle-D-Arg- NH(2) (ffir-NH(2)), through central (i.c.v.) or peripheral (i.p.) routes of administration. Locomotor activity was assessed via activity monitoring chambers and rotorod. Cognitive performance was assessed in a novel object recognition task. Prolonged hypolocomotion was observed following administration of 1.0 and 10.0, but not 0.3 mg/kg U50,488. Central, but not peripheral, administration of ffir-NH(2) (a KOR agonist that does not cross the blood-brain barrier) also reduced motor behavior. Systemic pretreatment with the low dose of U50,488 (0.3 mg/kg, i.p.) significantly impaired performance in the novel object recognition task. Likewise, ffir-NH(2) significantly reduced novel object recognition after central (i.c.v.), but not peripheral (i.p.), administration. U50,488- and ffir-NH(2)-mediated deficits in novel object recognition were prevented by pretreatment with KOR antagonists. Cocaine-induced conditioned place preference was subsequently assessed and was reduced by pretreatment with U50,488 (0.3 mg/kg, i.p.). Together, these results suggest that the activation of centrally-located kappa opioid receptors may induce cognitive and mnemonic disruption independent of hypolocomotor effects which may contribute to the KOR-mediated suppression of psychostimulant reward.

Cocaine dependence is an enduring problem and years of research and drug development has yet to produce an efficacious pharmacotherapy. Recent clinical research suggests that chronic treatment with amphetamine-like medications produces tolerance to cocaine's reinforcing effects and may offer a viable pharmacotherapy. Three methamphetamine-dependent participants that had been in our clinical laboratory experiments and previously addicted to cocaine are reviewed. Data obtained from initial screen and informal conversation suggested that all participants considered methamphetamine to have helped them stop using cocaine and eliminate cocaine craving. Methamphetamine also significantly decreased their alcohol consumption but did not alter cannabis or nicotine use.

Prenatal exposure to alcohol is associated with cognitive abnormalities that persist throughout the lifespan and are also often a focus of studies examining cognitive outcomes associated with excessive alcohol use by an individual. This study examined the effect of birth outcomes consistent with fetal alcohol exposure on associations between lifetime alcohol dependence and cognition in middle adulthood. The sample was comprised of 315 adult adoptees ranging in age from 31 to 64 years (SD = 7.20). Facial morphology, pre-morbid cognition, and current cognition were assessed. Birth parent behaviors and birth outcomes (e.g., birthweight, gestational age) were obtained from adoption agency records. Lifetime alcohol dependence was determined from the Semi-Structured Assessment of the Genetics of Alcoholism - II. Univariate associations showed significantly poorer pre-morbid and current cognition when birth parent problems, short palpebral fissures, and thin upper lips were present. Lifetime alcohol dependence was associated with lower perceptional organization, processing speed and working memory. Multivariate analyses demonstrated continued significance suggesting unique contributions of each to cognition. Evaluating the possible role of fetal alcohol exposure within studies on alcoholism can only further improve the treatment and prevention of alcohol-related problems by isolating those cognitive outcomes uniquely attributable to an individual's consumption of alcohol.

OBJECTIVES: Both hangover and performance deficits have been documented the day after drinking to intoxication after breath alcohol concentration (BrAC) has returned to near zero. But few studies have examined the relationship between hangover and post-intoxication performance. METHOD: We performed secondary analyses of data from a previously reported controlled cross-over laboratory study to assess the relationship of hangover incidence and severity to sustained attention/reaction time the morning after drinking to about 0.11 g% BrAC. Relationships were investigated while controlling for gender, type of alcoholic beverage (bourbon or vodka), and neurocognitive performance after placebo. RESULTS: Hangover severity and neurocognitive performance were significantly correlated. Participants reporting stronger hangover were more impaired than those reporting little or no hangover. Comparing any to no hangover showed a trend in the same direction of effect. CONCLUSIONS: More intense hangover may indicate less fitness for duty in workers in certain safety-sensitive occupations, with implications for occupational alcohol policies.