Increased Serum Brain-Derived Neurotrophic Factor Is Predictive of Cocaine Relapse Outcomes: A Prospective Study

D’Sa, Carrol; Fox, Helen; Hong, Adam K.; DiLeone, Ralph J.; Sinha, Rajita

doi:10.1016/j.biopsych.2011.05.013

Cited by 63 publications

(59 citation statements)

References 35 publications

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“…Our finding of sustained elevation of BDNF plasma levels in women with cocaine dependence is consistent with those of many previous clinical and preclinical reports. 4,6,17,19 A consistent body of evidence stemming from rat models has indicated that elevated BDNF plays an important role in the enhancement of mesolimbic DA neuronal function, which could be related both to increased drug seeking behaviour/ craving and to the reward effect of the drug. 47 The role of DA is primarily in the reinforcing effects of drugs and the motivation to obtain them.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4] Because preclinical evidence has suggested a potential role of these endogenous peptides in mediating the behavioural effects related to substance administration 5 and drug-induced neuro adaptation, 6 recent studies have explored neurotrophin expression in humans 4,7,8 to better comprehend the neurobiological and circuit underpinnings of addiction.…”

Section: Introductionmentioning

confidence: 99%

“…17,18 Furthermore, recent studies have shown a significant increase in BDNF levels over the first days of cocaine abstinence in both preclinical and clinical models, which is most likely due to compensatory mechanisms activated in response to the neurotoxic effects of chronic cocaine exposure. 4,19 Levels of BDNF following cocaine detoxification also have predictive value for the loss of control measures affecting craving and relapse. 2,8 However, contrary to the BDNF findings, data from human and animal studies have shown decreased NGF levels after both heroin and cocaine withdrawal.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

Viola

Tractenberg

Levandowski

et al. 2014

J Psychiatry Neurosci

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

Viola

Tractenberg

Levandowski

et al. 2014

J Psychiatry Neurosci

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“…The first study assessing BDNF in cocaine addicts found no difference in BDNF serum levels in 15 cocaine addicts and a group of healthy controls (Angelucci et al, 2007). However, a recent cross-sectional study of 22 cocaine-dependent individuals reported a significant correlation between serum BDNF and number of abstinence days (Hilburn et al, 2011) and recently, BDNF was reported to be increased after 3 weeks of withdrawal (D'Sa et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence

Corominas-Roso

Roncero

Eiroá-Orosa

et al. 2013

European Neuropsychopharmacology

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Cite as: Corominas-Roso, M., Roncero, C., Eiroa-Orosa, F. J., Gonzalvo, B., Grau-Lopez, L., Ribases, M., … Casas, M. (2013). Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence. European Neuropsychopharmacology, 23(9) completed a two-week detoxification program at an inpatient facility. Two serum samples were collected for each patient at baseline and at the end of the protocol.Serum samples were also collected for 46 healthy controls (aged 35.52 ± 9.37 years).Demographic, consumption and clinical data were recorded for all patients.Significantly lower serum BDNF levels (p<.0001) were observed for cocaine-dependent patients at baseline compared to healthy controls. Serum BDNF levels increased significantly across 12 days of early abstinence (p = .030). Baseline BDNF levels correlated with craving (p = .034). Post-detoxification BDNF levels correlated with craving (p = .018), loss of control (p < .000), abstinence measures (p = 0.031), depression (p = 0.036), and anxiety (p = 0.036). Post-detoxification BDNF levels also had predictive value for the loss of control measure of craving. Chronic cocaine use is associated with decreased serum BDNF. A progressive increase in serum BDNF levels during early abstinence correlates with cocaine craving and abstinence symptoms and may reflect increasing BDNF levels in different brain regions. These findings suggest that serum BDNF may be a biomarker for cocaine addiction.

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“…In support of this idea, available evidence indicates that in recovering cocaine-dependent individuals, elevated BDNF serum levels predicted shorter subsequent time to relapse, higher total cocaine use, and cocaine craving (D'Sa et al 2011;Corominas-Roso et al 2012). In conjunction, laboratory animals display a progressive increase in Bdnf protein levels in mesolimbic areas, including the PFC (Grimm et al 2003;McGinty et al 2010;Pickens et al 2011) following prolonged abstinence.…”

Section: Neurobiology Of Cocaine Addictionmentioning

confidence: 93%

The Efficacy of Exercise to Attenuate Cocaine Relapse is Associated with Changes in Bdnf and Altered by Sex and Estrous Cycle Phase.

Peterson

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Exercise is a potential intervention for cocaine addiction that has shown promise in both human and animal studies. However, the conditions that produce the most efficacious response have yet to be determined. Thus, the goal of this dissertation is to determine the exercise conditions that produce the most efficacious response in a preclinical model of cocaine addiction. The overall hypothesis is that exercise will be an effective intervention that reduces cocaine relapse vulnerability and blocks subsequent neuroadaptations that develop over an abstinence period. Although exercise is known to induce widespread effects in the brain and act on many different signaling pathways (e.g., norepinephrine, opioid, serotonin, endocannabinoid, cortisol); this dissertation will focus on its effects on brain derived neurotrophic factor (Bdnf) exon IV expression in the prefrontal cortex (PFC) as potential mechanism given that it is a marker of epigenetic regulation implicated in cocaine relapse and known to be regulated by exercise.Chapter I of this dissertation provides background on the behavior and underlying neurobiology (i.e. epigenetic regulation of Bdnf) of cocaine addiction. This chapter also provides evidence to support the hypothesis that the efficacy of exercise for preventing relapse vulnerability is associated with alterations in Bdnf expression. Chapter II demonstrates that the efficacy of wheel running, an animal model of exercise, is dosedependent, with greatest effects following longer access, and is associated with epigenetic regulation of Bdnf exon IV expression in the PFC. Chapter III demonstrates that early, but not late, access to a running wheel during abstinence attenuates subsequent cocaine-seeking. Chapter IV demonstrates that the efficacy of wheel running is iii influenced by sex, estrous cycle phase, and dose conditions. In this chapter I demonstrate that males are more sensitive to the beneficial effects of wheel running, while in females longer access conditions is required to override estrus-induced vulnerability. Overall, the data presented in this dissertation establishes exercise as a promising intervention that has the ability to reduce cocaine relapse vulnerability likely by blocking cocaine-induced neuroadaptations (e.g. Bdnf) that develop over an abstinence period.

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Increased Serum Brain-Derived Neurotrophic Factor Is Predictive of Cocaine Relapse Outcomes: A Prospective Study

Cited by 63 publications

References 35 publications

Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

Neurotrophic factors in women with crack cocaine dependence during early abstinence: the role of early life stress

Brain-derived neurotrophic factor serum levels in cocaine-dependent patients during early abstinence

The Efficacy of Exercise to Attenuate Cocaine Relapse is Associated with Changes in Bdnf and Altered by Sex and Estrous Cycle Phase.

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