Long-Term frontal brain metabolic changes in cocaine abusers

Brookhaven National Laboratory, Upton, New York 11973.
Synapse (Impact Factor: 2.13). 07/1992; 11(3):184-90. DOI: 10.1002/syn.890110303
Source: PubMed

ABSTRACT Neurological complications from cocaine use are well recognized. We propose that chronic cocaine use can also cause clinically silent brain dysfunction.
We investigated brain glucose metabolism with positron emission tomography (PET) and 2-deoxy-2[18F] fluoro-D-glucose (FDG) in 21 neurologically intact chronic cocaine abusers (C) and 18 normal controls (N). The cocaine abusers were tested 1–6 weeks after the last use of cocaine and seven were retested after a 3 month drug-free period.
Global cerebral glucose metabolism was not significantly different between controls and cocaine abusers (N = 38.4±3, C = 36.5±5 μmol/100 g of tissue, min). However, cocaine abusers had significantly (P< 0.05) lower metabolic activity in 16 of the 21 left frontal regions and 8 of the 21 right frontal regions. These decreases persisted after 3–4 months of detoxification and were correlated with the dose (P ≤ 0.01) and the years of cocaine use (P ≤ 0.05).
This study shows reduced rates of frontal metabolism in neurologically intact cocaine abusers that persist even after 3–4 months of detoxification. © Wiley-Liss, Inc.

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    • "Furthermore, cocaine users exhibit impaired cognitive control and increased impulsivity (Goldstein and Volkow, 2002; Kjome et al., 2010; Lane et al., 2007), as well as decreased sensorimotor performance (Hanlon et al., 2009, 2010), suggesting a broad range of consequences from long-term cocaine exposure. These impairments are accompanied by alterations in the regulation of transmitter systems (Volkow et al., 2006; Martinez et al., 2004; Mash et al., 2002, 2005), reductions in functional activity in the prefrontal cortex (Volkow et al., 1992), decreases in gray matter volume (Hanlon et al., 2011; Matochik et al., 2003; Fein et al., 2002; Lim et al., 2008), and reductions in the integrity of white matter (Franklin et al., 2002; Lim et al., 2002; Ma et al., 2009; Moeller et al., 2005) among many other deficits when compared to healthy controls. Studies, particularly those in animal models, have shown that many of these abnormalities result from repeated exposure to cocaine, and are not merely the result of conditions that pre-date drug use. "
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    ABSTRACT: Cocaine users exhibit a wide range of behavioral impairments accompanied by brain structural, neurochemical and functional abnormalities. Metabolic mapping studies in cocaine users and animal models have shown extensive functional alterations throughout the striatum, limbic system, and cortex. Few studies, however, have evaluated the persistence of these effects following cessation of cocaine availability. The purpose of this study, therefore, was to assess the functional effects of re-exposure to cocaine in nonhuman primates after the discontinuation of cocaine self-administration for 30 or 90 days, using the quantitative autoradiographic 2-[(14)C]deoxyglucose (2DG) method. Rhesus monkeys self-administered cocaine (fixed interval 3-min schedule, 30 infusions per session, 0.3 mg/kg/infusion) for 100 sessions followed by 30 (n=4) or 90 days (n=3) during which experimental sessions were not conducted. Food-reinforced control animals (n=5) underwent identical schedules of reinforcement. Animals were then re-exposed to cocaine or food for one final session and the 2DG method applied immediately after session completion. Compared to controls, re-exposure to cocaine after 30 or 90 day drug-free periods resulted in lower rates of glucose utilization in ventral and dorsal striatum, prefrontal and temporal cortex, limbic system, thalamus, and midbrain. These data demonstrate that vulnerability to the effects of cocaine persists for as long as 90 days after cessation of drug use. While there was some evidence for recovery (fewer brain areas were affected by cocaine re-exposure at 90 days as compared to 30 days), this was not uniform across regions, thus suggesting that recovery occurs at different rates in different brain systems.
    Neuropharmacology 06/2014; 85. DOI:10.1016/j.neuropharm.2014.06.003 · 5.11 Impact Factor
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    • "Neuroimaging studies suggest that decreased dopamine-related activation of reward circuits may account for hypoactivation in the ACC (Volkow et al. 1993). Our finding of decreased ACC activation in former users is consistent with reports in the literature that cocaine abusers show reduced ACC activation 3 to 4 months after withdrawal (Volkow et al. 1992) and neuropsychological deficits up to 6 months of abstinence (Bolla et al. 2000; Di Sclafani et al. 2002; van Gorp et al. 1999). HIV-infected individuals with and without a history of cocaine abuse show decreased dopamine transporters in the dorsal striatum, and this reduction Table 3 Group differences in activation during encoding and recognition: brain region, Brodmann area (BA), SPM coordinates, cluster size (k), and statistical information Brain region BA Coordinates (x, y, z) "
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    • "Increasing evidence has suggested that poor inhibitory control resulting from sub-optimal functioning of prefrontal cortical structures (Volkow & Fowler, 2000; Naqvi & Bechara, 2009; Ersche et al., 2012) that may precede (Volkow & Fowler, 2000; Ersche et al., 2012), or be the result of, chronic exposure to addictive drugs may provide an important mechanism underlying the propensity to lose control over drug intake and to seek cocaine compulsively (Volkow et al., 1992; Grant et al., 1996; Rogers et al., 1999; Hester & Garavan, 2004; Ersche et al., 2005). Individuals addicted to cocaine or other drugs of abuse show decreased grey matter volume in several subregions of the prefrontal cortex (PFC), including the orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and insular cortex (IC) (Franklin et al., 2002; Matochik et al., 2003; Ersche et al., 2011, 2012), as well as alterations in the amygdala, albeit with less consistent findings (Makris et al., 2004; Ersche et al., 2012), and white matter changes suggesting disrupted connectivity between cortical and striatal structures (Ersche et al., 2012). "
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    ABSTRACT: Compulsive drug use and a persistent vulnerability to relapse are key features of addiction. Imaging studies have suggested that these features may result from deficits in prefrontal cortical structure and function, and thereby impaired top-down inhibitory control over limbic-striatal mechanisms of drug-seeking behaviour. We tested the hypothesis that selective damage to distinct subregions of the prefrontal cortex, or to the amygdala, after a short history of cocaine taking would: (i) result in compulsive cocaine seeking at a time when it would not usually be displayed; or (ii) facilitate relapse to drug seeking after abstinence. Rats with selective, bilateral excitotoxic lesions of the basolateral amygdala or anterior cingulate, prelimbic, infralimbic, orbitofrontal or anterior insular cortices were trained to self-administer cocaine under a seeking-taking chained schedule. Intermittent mild footshock punishment of the cocaine-seeking response was then introduced. No prefrontal cortical lesion affected the ability of rats to withhold their seeking responses. However, rats with lesions to the basolateral amygdala increased their cocaine-seeking responses under punishment and were impaired in their acquisition of conditioned fear. Following a 7-day abstinence period, rats were re-exposed to the drug-seeking environment for assessment of relapse in the absence of punishment or cocaine. Rats with prelimbic cortex lesions showed decreased seeking responses during relapse, whereas those with anterior insular cortex lesions showed an increase. Combined, these results show that acute impairment of prefrontal cortical function does not result in compulsive cocaine seeking after a short history of self-administering cocaine, but further implicates subregions of the prefrontal cortex in relapse.
    European Journal of Neuroscience 07/2013; 38(7). DOI:10.1111/ejn.12289 · 3.18 Impact Factor
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