Adrenal Activity during Repeated Long-Access Cocaine Self-Administration is Required for Later CRF-Induced and CRF-Dependent Stressor-Induced Reinstatement in Rats

Graf, Evan N.; Hoks, Michael A.; Baumgardner, Jean; Sierra, J. F. Rodriguez; Vranjkovic, Oliver; Bohr, Colin; Baker, David L.; Mantsch, John R.

doi:10.1038/npp.2011.28

Cited by 32 publications

(34 citation statements)

References 81 publications

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“…We conclude that corticosterone-induced inhibition of dopamine clearance increases sensitivity to the effects of cocaine on dopaminergic neurotransmission and behavior and may represent a fundamental mechanism through which stress modulates dopaminergic neurotransmission, resulting in alterations in motivated behavior. Although acute stress can, under certain conditions, act as a primary trigger for the reinstatement of drug-seeking behavior (Erb et al, 1998;Graf et al, 2011), it has been proposed that stress more often acts as a "stage-setter," increasing the likelihood of relapse in response to other drug-associated stimuli (Preston and Epstein, 2011). The present studies model the stage-setting actions of stress and demonstrate that, even under conditions when stress alone does not trigger reinstatement, it can potentiate reinstatement in response to another subthreshold stimulus.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, reinstatement induced primarily by stress does not require increases in corticosterone to stress levels (Erb et al, 1998;Graf et al, 2011). In contrast, the potentiation of cocaine-induced reinstatement by stress requires elevation of corticosterone to stress levels, and treatment with stress levels of corticosterone in the absence of stress is sufficient to potentiate cocaine-induced reinstatement.…”

Section: Discussionmentioning

confidence: 99%

“…Rats received indwelling jugular catheters under ketamine/xylazine (100 mg/kg; 2 mg/kg, i.p.) anesthesia as previously described (Graf et al, 2011). Lines were connected to syringe pumps (Razel) via fluid swivels (Instech Laboratory) suspended above the chambers.…”

Section: Methodsmentioning

confidence: 99%

“…In human addicts, stress-, cue-, and drug-induced craving for cocaine is associated with elevated cortisol (Berger et al, 1996;Reid et al, 2003;Sinha et al, 2003) and heightened HPA reactivity can predict relapse susceptibility (Sinha et al, 2006Fatseas et al, 2011;McKee et al, 2011). In rodents, glucocorticoids can enhance behavioral and neurochemical responses to drugs of abuse Marinelli et al, 1997;Barrot et al, 2000), but eliminating increases in glucocorticoids does not prevent stress-or cocaineinduced reinstatement of compulsive drug seeking in rats (Erb et al, 1998;Mantsch et al, 2008;Graf et al, 2011) or cocaineinduced reinstatement in monkeys (Lee et al, 2003), and studies examining the ability of elevated glucocorticoids alone to reinstate cocaine seeking have yielded mixed results (Deroche et al, 1997; Lee et al, 2003;Shalev et al, 2003). Together, these studies indicate that, although glucocorticoids alone may not drive relapse, they do interact with drugs and drug-associated stimuli to influence the likelihood of drug use.…”

Section: Introductionmentioning

confidence: 99%

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Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Graf

Wheeler

Baker

et al. 2013

Journal of Neuroscience

126

134

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Stressful life events are important contributors to relapse in recovering cocaine addicts, but the mechanisms by which they influence motivational systems are poorly understood. Studies suggest that stress may "set the stage" for relapse by increasing the sensitivity of brain reward circuits to drug-associated stimuli. We examined the effects of stress and corticosterone on behavioral and neurochemical responses of rats to a cocaine prime after cocaine self-administration and extinction. Exposure of rats to acute electric footshock stress did not by itself reinstate drug-seeking behavior but potentiated reinstatement in response to a subthreshold dose of cocaine. This effect of stress was not observed in adrenalectomized animals, and was reproduced in nonstressed animals by administration of corticosterone at a dose that reproduced stress-induced plasma levels. Pretreatment with the glucocorticoid receptor antagonist RU38486 did not block the corticosterone effect. Corticosterone potentiated cocaine-induced increases in extracellular dopamine in the nucleus accumbens (NAc), and pharmacological blockade of NAc dopamine receptors blocked corticosterone-induced potentiation of reinstatement. Intraaccumbens administration of corticosterone reproduced the behavioral effects of stress and systemic corticosterone. Corticosterone treatment acutely decreased NAc dopamine clearance measured by fast-scan cyclic voltammetry, suggesting that inhibition of uptake 2 -mediated dopamine clearance may underlie corticosterone effects. Consistent with this hypothesis, intra-accumbens administration of the uptake 2 inhibitor normetanephrine potentiated cocaine-induced reinstatement. Expression of organic cation transporter 3, a corticosterone-sensitive uptake 2 transporter, was detected on NAc neurons. These findings reveal a novel mechanism by which stress hormones can rapidly regulate dopamine signaling and contribute to the impact of stress on drug intake.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Graf

Wheeler

Baker

et al. 2013

Journal of Neuroscience

126

134

View full text Add to dashboard Cite

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“…Reinstatement sessions were identical to extinction sessions except that they were preceded by exposure to shock and/or intracranial drug delivery. Shocks (0.5 mA, 0.5 s duration) were delivered on average every 40 s (range, 10 -70 s) through the grid floors of the chambers over a 15 min period that immediately preceded the 2 h reinstatement test session (Blacktop et al, 2011;Graf et al, 2011). During the shock session, the levers were retracted and the stimulus lights were off, but a houselight in the chamber was illuminated.…”

Section: Extinction Training and Reinstatement Testingmentioning

confidence: 99%

Stress-Induced Cocaine Seeking Requires a Beta-2 Adrenergic Receptor-Regulated Pathway from the Ventral Bed Nucleus of the Stria Terminalis That Regulates CRF Actions in the Ventral Tegmental Area

et al. 2014

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The ventral bed nucleus of the stria terminalis (vBNST) has been implicated in stress-induced cocaine use. Here we demonstrate that, in the vBNST, corticotropin releasing factor (CRF) is expressed in neurons that innervate the ventral tegmental area (VTA), a site where the CRF receptor antagonist antalarmin prevents the reinstatement of cocaine seeking by a stressor, intermittent footshock, following intravenous self-administration in rats. The vBNST receives dense noradrenergic innervation and expresses ␤ adrenergic receptors (ARs). Footshock-induced reinstatement was prevented by bilateral intra-vBNST injection of the ␤-2 AR antagonist, ICI-118,551, but not the ␤-1 AR antagonist, betaxolol. Moreover, bilateral intra-vBNST injection of the ␤-2 AR agonist, clenbuterol, but not the ␤-1 agonist, dobutamine, reinstated cocaine seeking, suggesting that activation of vBNST ␤-2 AR is both necessary for stress-induced reinstatement and sufficient to induce cocaine seeking. The contribution of a ␤-2 AR-regulated vBNST-to-VTA pathway that releases CRF was investigated using a disconnection approach. Injection of ICI-118,551 into the vBNST in one hemisphere and antalarmin into the VTA of the contralateral hemisphere prevented footshock-induced reinstatement, whereas ipsilateral manipulations failed to attenuate stressinduced cocaine seeking, suggesting that ␤-2 AR regulate vBNST efferents that release CRF into the VTA, activating CRF receptors, and promoting cocaine use. Last, reinstatement by clenbuterol delivered bilaterally into the vBNST was prevented by bilateral vBNST pretreatment with antalarmin, indicating that ␤-2 AR-mediated actions in the vBNST also require local CRF receptor activation. Understanding the processes through which stress induces cocaine seeking should guide the development of new treatments for addiction.

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Glucocorticoid Involvement in Drug Abuse and Addiction

Mantsch

Gasser

2015

Neuroendocrinology of Stress

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Adrenal Activity during Repeated Long-Access Cocaine Self-Administration is Required for Later CRF-Induced and CRF-Dependent Stressor-Induced Reinstatement in Rats

Cited by 32 publications

References 81 publications

Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Corticosterone Acts in the Nucleus Accumbens to Enhance Dopamine Signaling and Potentiate Reinstatement of Cocaine Seeking

Stress-Induced Cocaine Seeking Requires a Beta-2 Adrenergic Receptor-Regulated Pathway from the Ventral Bed Nucleus of the Stria Terminalis That Regulates CRF Actions in the Ventral Tegmental Area

Glucocorticoid Involvement in Drug Abuse and Addiction

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