Cocaine abusers demonstrate faulty decision-making as manifested by their inability to discontinue self-destructive drug-seeking behaviors. The orbitofrontal cortex (OFC) plays an important role in decision-making. In this preliminary study we tested whether 25-day-abstinent cocaine abusers show alterations in normalized cerebral blood flow (rCBF) in the OFC using PET with 15 O during the Iowa Gambling Task (a decision-making task). This task measures the ability to weigh short-term rewards against long-term losses. A control task matched the sensorimotor aspects of the task but did not require decision-making. Cocaine abusers (N = 13) showed greater activation during performance of the Iowa Gambling Task in the right OFC and less activation in the right dorsolateral prefrontal cortex (DLPFC) and left medial prefrontal cortex (MPFC) compared to a control group (N = 13). Better Iowa Gambling Task performance was associated with greater activation in the right OFC in both groups. Also, the amount of cocaine used (grams/week) prior to the 25 days of enforced abstinence was negatively correlated with activation in the left OFC. Greater activation in the OFC in cocaine abusers compared to a control group may reflect differences in the anticipation of reward while less activation in the DLPFC and MPFC may reflect differences in planning and working memory. These findings suggest that cocaine abusers show persistent functional abnormalities in prefrontal neural networks involved in decision-making and these effects are related to cocaine abuse. Compromised decision-making could contribute to the development of addiction and undermine attempts at abstinence.

The anterior cingulate cortex (ACC) and lateral prefrontal (LPFC) cortex are brain regions important to executive cognitive functions (ECF). We determined ACC and LPFC function in 23-day abstinent cocaine abusers using positron emission tomography (PET H 2 15 O) during performance of a modified version of the Stroop Task. Cocaine abusers showed less activation than non-drug-using comparison subjects in the left ACC and the right LPFC and greater activation in the right ACC. Average amount of cocaine used per week was negatively correlated with activity in the rostral ACC and right LPFC. Disruption of ECF in substance abusers could interfere with attempts to stop drug use and undermine treatment. Since impairment in ECF may be a common feature of various neuropsychiatric disorders, these findings have applicability beyond the neurobiology of addiction.Cocaine abuse is a substantial public health concern, as recent estimates indicate that there are 1.5 million chronic cocaine users in the United States. 1 Societal costs of drug abuse including cocaine abuse are estimated to be $62 billion. 2 The use of cocaine produces changes in brain chemistry with attendant functional consequences. Neuroimaging studies have revealed metabolic 3,4 and structural 5 differences in prefrontal brain regions, including the anterior cingulate cortex (ACC) and lateral prefrontal cortex (LPFC) of cocaine and polydrug abusers relative to non-drug-using comparison subjects. The caudal-dorsal ACC has strong reciprocal interconnections with the LPFC, and this network operates during performance of tasks that involve high levels of mental effort. 6 This neural network also appears to participate in executive cognitive functions (ECF) governing resolution of conflict, response inhibition, performance monitoring, implementation of control, and error monitoring. [7][8][9][10][11] Disruption of these functions could impair an individual's ability to monitor and inhibit inappropriate behavior. In the context of substance abuse, such disruption could impede the discontinuation of self-destructive, drug seeking behavior, thereby undermining treatment.The aim of this investigation was to determine if cocaine abusers have impaired function of the ACC and LPFC. We used water method positron emission tomography (PET H 2 15 O) imaging and a cognitive activation task, a modified version of the Stroop Task. 12 9,10,17,18 The LPFC plays a role in maintaining attentional demands of the Stroop Task whereas the ACC plays a role in conflict monitoring. 10 It is important to study the functional integrity of the ACC and LPFC in cocaine abusers because dysregulation of this prefrontal neural network might contribute to the development and persistence of maladaptive behaviors (e.g., poor response selection) that could sustain addiction or impede abstinence from drug use.In previous neurobehavioral studies of abstinent cocaine abusers, we have shown a dose-related relationship between the amount of cocaine used and performance on tasks associated with ACC ...

Summary Background Progesterone, a steroid hormone, has been implicated in many CNS functions including reward, cognition, and neuroprotection. The goal of this study was to examine the dose-dependent effects of progesterone on cognitive performance, smoking urges, and smoking behavior in smokers. Methods Thirty female and thirty-four male smokers participated in a double-blind, placebo-controlled study. Female smokers were in the early follicular phase of their menstrual cycle during study participation. Smokers were randomly assigned to either 200 or 400 mg/day of progesterone or placebo, given in two separate doses, during clinic visit. The first 3 days of the treatment period, smokers abstained from smoking, which was verified with breath CO levels. Smokers attended an experimental session on day 4 where the number of cigarettes smoked were recorded starting two hours after the medication treatment. Results Progesterone treatment, 200 mg/day, significantly improved cognitive performance in the Stroop and the Digit Symbol Substitution Test. Progesterone at 400 mg/day was associated with reduced urges for smoking but did not change ad lib smoking behavior. Conclusions These findings suggest a potential therapeutic value of progesterone for smoking cessation.

These results suggest that topiramate may enhance the subjective effects of nicotine and attenuate the heart rate response to nicotine. While the exact mechanisms are unclear, enhancement of the dopaminergic system and attenuation of the noradrenergic system may mediate the topiramate's effects on the subjective and cardiovascular responses to nicotine, respectively. The utility of topiramate for smoking cessation needs to be examined further in controlled clinical trials.