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A defining feature of drug addiction is persistent drug use despite long-term adverse consequences. This study examined the performance of drug abusers on a neuropsychological test that requires evaluation of long-term outcomes in the presence of a complex set of mixed reward/punishment contingencies (the Gambling Task). In order to control for generalized(More)
The induction of programmed cell death, or apoptosis, involves activation of a signalling system, many elements of which remain unknown. The sphingomyelin pathway, initiated by hydrolysis of the phospholipid sphingomyelin in the cell membrane to generate the second messenger ceramide, is thought to mediate apoptosis in response to tumour-necrosis factor(More)
Evidence accumulated over more than 45 years has indicated that environmental stimuli can induce craving for drugs of abuse in individuals who have addictive disorders. However, the brain mechanisms that subserve such craving have not been elucidated. Here a positron emission tomographic study shows increased glucose metabolism in cortical and limbic(More)
We have extended our previous work investigating the neural correlates of cue-induced cocaine craving through the use of positron emission tomography with greater spatial resolution (<4.6 mm), an evocative script, and a pixel-by-pixel analysis. Craving and cerebral glucose metabolism were measured after presentation of cocaine-related or neutral cues to 11(More)
Extensive literature has linked behavior control problems in childhood to risk for alcoholism, but impulsivity in alcohol-dependent adults has not been well characterized. Using a variety of laboratory measures of impulsivity, we assessed whether detoxified alcohol-dependent patients [(ADP); n = 130] were more impulsive than control subjects [(CS); n = 41].(More)
The DNA damage response (DDR) represents a complex network of multiple signaling pathways involving cell cycle checkpoints, DNA repair, transcriptional programs, and apoptosis, through which cells maintain genomic integrity following various endogenous (metabolic) or environmental stresses. In cancer treatment, the DDR occurs in response to various(More)
The Bcl-2 antagonist ABT-737 targets Bcl-2/Bcl-xL but not Mcl-1, which may confer resistance to this novel agent. Here, we show that Mcl-1 down-regulation by the cyclin-dependent kinase (CDK) inhibitor roscovitine or Mcl-1-shRNA dramatically increases ABT-737 lethality in human leukemia cells. ABT-737 induces Bax conformational change but fails to activate(More)
Within the last 15 years, multiple new signal transduction pathways within cells have been discovered. Many of these pathways belong to what is now termed ‘the mitogen-activated protein kinase (MAPK) superfamily.' These pathways have been linked to the growth factor-mediated regulation of diverse cellular events such as proliferation, senescence,(More)
OBJECTIVE The study assessed the validity of the Gambling Task as a test of decision-making ability in adolescents and examined whether adolescents with behavior disorders, who are at risk for substance abuse, have deficits in decision making similar to those exhibited by adults with substance abuse. METHOD Performance on the Gambling Task in two testing(More)
This article examines the theoretical basis of decision-making deficits exhibited by cocaine abusers in a laboratory decision-making task first described by Bechara, Damasio, Damasio, and Anderson (1994). A total of 12 male cocaine abusers and 14 comparison subjects performed the task, and the cocaine group performed significantly worse than the comparison(More)