Stress-Induced Cocaine Craving and Hypothalamic-Pituitary-Adrenal Responses Are Predictive of Cocaine Relapse Outcomes

Sinha, Rajita; García, Miguel; Paliwal, Prashni; Kreek, Mary Jeanne; Rounsaville, Bruce J.

doi:10.1001/archpsyc.63.3.324

Cited by 488 publications

(418 citation statements)

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“…Stressful imagery has been reported to elicit drug craving in abstinent cocaine users (Fox et al, 2005). Moreover, using the same procedure, an inverse relationship between stress-induced cocaine craving and time to relapse, as well as a positive relationship between stress-induced cortisol levels and drug intake, during relapse, has been reported (Sinha et al, 2006). Data from animal models of relapse also support the importance of stress in reinstating previously extinguished drug-seeking behavior (see Shaham et al, 2000 for a review) and, in the case of heroin, rats with long (11-h) access exhibit greater levels of stress-induced reinstatement compared to those with short (1-h) access (Ahmed et al, 2000).…”

Section: Discussionmentioning

confidence: 89%

“…Thus, increased and persistent stress reactivity associated with a history of escalated cocaine self-administration suggests that increased sensitivity to stress induced by chronic cocaine may exacerbate the role of stress per se as a risk factor for relapse. Moreover, because stress also induces craving (Fox et al, 2005), a condition that has been shown to be predictive of shorter time to relapse and increased drug intake during relapse (Sinha et al, 2006), increased stress reactivity may further exacerbate the likelihood and severity of relapse associated with cocaine craving.…”

Section: Discussionmentioning

confidence: 99%

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Rats with Extended Access to Cocaine Exhibit Increased Stress Reactivity and Sensitivity to the Anxiolytic-Like Effects of the mGluR 2/3 Agonist LY379268 during Abstinence

Aujla

Martin‐Fardon

Weiss

2007

Neuropsychopharmacol

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Metabotropic glutamate 2/3 receptors (mGluR2/3) are emerging targets for the reduction of stress that contributes to drug relapse. The effect of a history of cocaine escalation on stress reactivity during abstinence and the role of mGlu2/3 receptors in stress in these animals were tested. Experiment 1FRats trained to self-administer cocaine, under short (ShA, 1-h) or long (LgA, 6-h) access conditions, or noncaloric food pellets (Ctrl, 1-h), were tested for stress reactivity in the shock-probe defensive burying test following 1, 14, 42, or 84 days of abstinence. Experiment 2FExperimentally naive rats receiving the mGlu2/3 receptor agonist LY379268 (0, 0.3, 1.0, or 3.0 mg/kg) were tested in the defensive burying test to establish the anxiolytic efficacy of this compound in this model. Experiment 3FRats with a history of ShA vs LgA cocaine self-administration, or a history of operant responding reinforced by noncaloric food pellets, were tested in the defensive burying test, following administration of LY379268 (0.3, 1.0, or 3.0 mg/kg) at 14 days of abstinence. LgA rats exhibited a two-to threefold increase in defensive burying at 1, 14, and 42 days of abstinence compared to ShA or control animals. LY379268 (3.0 mg/kg) reduced burying in all groups, whereas the 1.0-mg/kg dose reduced burying only in the LgA group. A robust and enduring increase in stress reactivity developed in rats with a history of daily 6-h access to cocaine. The anxiolytic-like effects of LY379268 identify mGlu2/3 receptors as targets for ameliorating stress-associated relapse risk, and point toward the possibility that a history of cocaine escalation in rats may modify glutamatergic function.

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Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Rats with Extended Access to Cocaine Exhibit Increased Stress Reactivity and Sensitivity to the Anxiolytic-Like Effects of the mGluR 2/3 Agonist LY379268 during Abstinence

Aujla

Martin‐Fardon

Weiss

2007

Neuropsychopharmacol

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“…Indeed, even after a period of abstinence, dependent individuals remain vulnerable to stress and other craving-inducing stimuli [10], which, in turn, leads to intense physiological responses and various negative feelings such as anger and sadness [11]. Real-time daily monitoring of craving and drug use has shown that craving reliably predicts relapse among dependent individuals [9,[12][13][14][15]. The data suggest that improving the treatment of craving could not only help prevent relapse, but could also reduce patient distress on the emotional, cognitive, and physiological levels.…”

Section: Overview Of Addiction and Current Treatment Challengesmentioning

confidence: 99%

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

et al. 2015

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Multiple cannabinoids derived from the marijuana plant have potential therapeutic benefits but most have not been well investigated, despite the widespread legalization of medical marijuana in the USA and other countries. Therapeutic indications will depend on determinations as to which of the multiple cannabinoids, and other biologically active chemicals that are present in the marijuana plant, can be developed to treat specific symptoms and/or diseases. Such insights are particularly critical for addiction disorders, where different phytocannabinoids appear to induce opposing actions that can confound the development of treatment interventions. Whereas Δ 9 -tetracannabinol has been well documented to be rewarding and to enhance sensitivity to other drugs, cannabidiol (CBD), in contrast, appears to have low reinforcing properties with limited abuse potential and to inhibit drug-seeking behavior. Other considerations such as CBD's anxiolytic properties and minimal adverse side effects also support its potential viability as a treatment option for a variety of symptoms associated with drug addiction. However, significant research is still needed as CBD investigations published to date primarily relate to its effects on opioid drugs, and CBD's efficacy at different phases of the abuse cycle for different classes of addictive substances remain largely understudied. Our paper provides an overview of preclinical animal and human clinical investigations, and presents preliminary clinical data that collectively sets a strong foundation in support of the further exploration of CBD as a therapeutic intervention against opioid relapse. As the legal landscape for medical marijuana unfolds, it is important to distinguish it from Bmedical CBD^and other specific cannabinoids, that can more appropriately be used to maximize the medicinal potential of the marijuana plant.

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“…However, other clinical studies have reported that after a brief period of abstinence, basal and corticotropin-releasing factor (CRF)-stimulated ACTH and cortisol levels in cocaine-dependent patients do not differ from those of healthy subjects (Mendelson et al, 1998;Jacobsen et al, 2001;Aouizerate et al, 2006). Psychological stressors or CRF elevate cocaine craving and HPA activity, and stress-induced ACTH and cortisol responses predict subsequent cocaine relapse (Sinha et al, 2006;Brady et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Persistent Increase in Hypothalamic Arginine Vasopressin Gene Expression During Protracted Withdrawal from Chronic Escalating-Dose Cocaine in Rodents

Zhou

Litvin

Piras

et al. 2011

Neuropsychopharmacol

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Arginine vasopressin (AVP) from the paraventricular nucleus (PVN) of hypothalamus has important roles in regulation of the hypothalamic-pituitary-adrenal (HPA) axis and stress-related behaviors during chronic stress. It is unknown, however, whether AVP in the PVN is involved in the modulation of HPA activity after chronic cocaine exposure. Here, we examined the gene expression alterations of AVP in the hypothalamus, and V1b receptor and pro-opiomelanocortin (POMC) in the anterior pituitary, as well as HPA hormonal changes, in Fischer rats after chronic cocaine and withdrawal, using two different chronic (14-day) 'binge' pattern administration regimens: steady-dose cocaine (SDC, 45 mg/kg/day) and escalating-dose cocaine (EDC, 45 up to 90 mg/kg/day). There was a significant (7-fold) plasma adrenocorticotropic hormone (ACTH) elevation after chronic EDC (but not SDC), coupled with increased V1b and POMC mRNA levels in the anterior pituitary. From acute (1-day) to protracted (14-day) withdrawal from chronic EDC (but not from SDC), we found persistent elevations of both plasma ACTH and corticosterone levels and AVP mRNA levels in the PVN. Selective V1b antagonist SSR149415 (5 mg/kg) attenuated acute withdrawal-induced HPA activation after EDC. To study potential roles of endogenous opioids in modulating the AVP gene, we administered naloxone (1 mg/kg); we found that opioid receptor antagonism increased AVP mRNA levels in cocaine-naive rats, but not in cocaine-withdrawn rats, suggesting less tonic opioid inhibition of PVN AVP neurons after chronic EDC. To assess the effects of cocaine withdrawal on sub-populations of PVN AVP neurons, we utilized AVP-enhanced green fluorescent protein (EGFP) promoter transgenic mice and found that acute withdrawal following chronic EDC increased the number of AVP-EGFP neurons in the parvocellular PVN (pPVN). These results suggest that during protracted withdrawal, enhanced pPVN AVP gene expression is associated with persistent elevations of basal HPA activity; a hyposensitivity of PVN AVP gene expression to naloxone is indicative of reduced opioidergic tone. Our studies indicate that the AVP and its V1b receptor system may be a potential therapeutic target for treating anxiety and depressive symptoms associated with cocaine addiction.

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Stress-Induced Cocaine Craving and Hypothalamic-Pituitary-Adrenal Responses Are Predictive of Cocaine Relapse Outcomes

Cited by 488 publications

References 50 publications

Rats with Extended Access to Cocaine Exhibit Increased Stress Reactivity and Sensitivity to the Anxiolytic-Like Effects of the mGluR 2/3 Agonist LY379268 during Abstinence

Rats with Extended Access to Cocaine Exhibit Increased Stress Reactivity and Sensitivity to the Anxiolytic-Like Effects of the mGluR 2/3 Agonist LY379268 during Abstinence

Early Phase in the Development of Cannabidiol as a Treatment for Addiction: Opioid Relapse Takes Initial Center Stage

Persistent Increase in Hypothalamic Arginine Vasopressin Gene Expression During Protracted Withdrawal from Chronic Escalating-Dose Cocaine in Rodents

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