Cocaine abuse remains a serious public-health concern in the United States. The propensity to binge use cocaine, and to combine it with other abused drugs, such as alcohol, heighten the health risks associated with cocaine use. Cocaine can impair several cognitive and mental processes, including those that control behavior. Thus, it is important to understand how such disturbances also can reduce control over cocaine intake once cocaine use has begun. The proposed project aims to determine how an inability to control cocaine consumption is linked to cocaine-induced impairment of inhibitory and activiational processes involved in the self-control and regulation of behavior. The project will test acute and chronic cocaine effects in adult cocaine abusers. The research combines measures of cocaine effects on cognitive inhibitory processes with conventional indices of abuse potential, based on subjective rewarding effects of the drug and its ability to reinforce self-administration. Initial studies will determine dose-response functions of cocaine on inhibitory control, and compare effects of different routes of administration. Subsequent studies will determine how inhibitory processes contribute to abuse potential by testing the degree to which acute cocaine-induced impairment of inhibitory control contributes to cocaine self-administration. The research also will determine how alcohol contributes to cocaine abuse potential by testing the degree to which its concomitant administration exacerbates cocaine-induced impairments of inhibitory control. Finally, the research will provide information on how long-term cocaine use could contribute to cognitive deficits that resemble attentional disorders, by producing a chronic deficit in basal levels of inhibitory control. The research has several long-term objectives. First, the findings and research strategies used to examine the role of cognitive mechanisms in cocaine abuse will allow the investigators to further develop and refine drug-testing protocols that measure the ability of medications to block the cognitive-impairing effects of cocaine which could play a role in its abuse potential. Second, the proposed research strategies and measures will provide initial methods and protocols for studying the combination of cocaine with other drugs of abuse that might also disrupt cognitive functions, such as opiates, which are also commonly co-administered with cocaine. Finally, the procedures for assessing inhibitory processes can be used to assess drug-free, basal levels of cognitive inhibitory functioning in drug abusers. Such studies would provide information on the degree to which these basic cognitive mechanisms play a role in the etiology of a general disinhibitory psychopathology which is considered to be a common phenotypic characteristic among drug abusers.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZDA1-MXV-P (04))
Program Officer
Schnur, Paul
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University of Kentucky
Schools of Arts and Sciences
United States
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Fillmore, Mark T; Rush, Craig R; Hays, Lon (2006) Acute effects of cocaine in two models of inhibitory control: implications of non-linear dose effects. Addiction 101:1323-32
Martin, Christopher S; Fillmore, Mark T; Chung, Tammy et al. (2006) Multidisciplinary perspectives on impaired control over substance use. Alcohol Clin Exp Res 30:265-71
Fillmore, Mark T; Rush, Craig R (2006) Polydrug abusers display impaired discrimination-reversal learning in a model of behavioural control. J Psychopharmacol 20:24-32
Fillmore, Mark T; Rush, Craig R; Abroms, Ben D (2005) d-Amphetamine-induced enhancement of inhibitory mechanisms involved in visual search. Exp Clin Psychopharmacol 13:200-8
Marczinski, Cecile A; Fillmore, Mark T (2005) Compensating for alcohol-induced impairment of control: effects on inhibition and activation of behavior. Psychopharmacology (Berl) 181:337-46
Fillmore, Mark T; Rush, Craig R; Hays, Lon (2005) Cocaine improves inhibitory control in a human model of response conflict. Exp Clin Psychopharmacol 13:327-35
Fillmore, Mark T; Kelly, Thomas H; Martin, Catherine A (2005) Effects of d-amphetamine in human models of information processing and inhibitory control. Drug Alcohol Depend 77:151-9
Abroms, Ben D; Fillmore, Mark T (2004) Alcohol-induced impairment of inhibitory mechanisms involved in visual search. Exp Clin Psychopharmacol 12:243-50
Fillmore, Mark T (2004) Environmental dependence of behavioral control mechanisms: effects of alcohol and information processing demands. Exp Clin Psychopharmacol 12:216-23
Marczinski, Cecile A; Fillmore, Mark T (2003) Preresponse cues reduce the impairing effects of alcohol on the execution and suppression of responses. Exp Clin Psychopharmacol 11:110-7

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