Increased cortisol levels are associated with low treatment retention in crack cocaine users

Ligabue, Karina Proença; Schuch, Jaqueline Bohrer; Scherer, Juliana Nichterwitz; Ornell, Felipe; Roglio, Vinícius Serafini; Assunção, Vanessa Aparecida Flores de; Rebelatto, Fernando Pezzini; Hildalgo, Maria Paz; Pechansky, Flávio; Kessler, Felipe; Diemen, Lísia von

doi:10.1016/j.addbeh.2019.106260

Cited by 13 publications

(16 citation statements)

References 45 publications

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“…Consistent with clinical reports that elevated cortisol levels can promote cocaine craving (Elman et al, 2003), are associated with poor cocaine use disorder treatment outcomes (Ligabue et al, 2020), and predict cocaine use (Sinha et al, 2006), we have identified a critical role for corticosterone in the stage setting effects of stress on cocaine seeking. The ability of footshock stress to potentiate cocaine-primed reinstatement is eliminated by prior surgical adrenalectomy (Graf et al, 2013) and reproduced in both rat selfadministration and mouse CPP models by administration of corticosterone, at a dose that results in plasma levels comparable to those observed following exposure to stressors (Graf et al, 2013;McReynolds et al, 2017).…”

Section: Role For Corticosteronesupporting

confidence: 87%

Neurochemical mechanisms and neurocircuitry underlying the contribution of stress to cocaine seeking

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Newenhizen

Mantsch

2021

Journal of Neurochemistry

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In individuals with substance use disorders, stress is a critical determinant of relapse susceptibility. In some cases, stressors directly trigger cocaine use. In others, stressors interact with other stimuli to promote drug seeking, thereby setting the stage for relapse. Here, we review the mechanisms and neurocircuitry that mediate stress-triggered and stress-potentiated cocaine seeking. Stressors trigger cocaine seeking by activating noradrenergic projections originating in the lateral tegmentum that innervate the bed nucleus of the stria terminalis to produce beta adrenergic receptor-dependent regulation of neurons that release corticotropin releasing factor (CRF) into the ventral tegmental area (VTA). CRF promotes the activation of VTA dopamine neurons that innervate the prelimbic prefrontal cortex resulting in D1 receptor-dependent excitation of a pathway to the nucleus accumbens core that mediates cocaine seeking. The stage-setting effects of stress require glucocorticoids, which exert rapid non-canonical effects at several sites within the mesocorticolimbic system. In the nucleus accumbens, corticosterone attenuates dopamine clearance via the organic cation transporter 3 to promote dopamine signaling. In the prelimbic cortex, corticosterone mobilizes the endocannabinoid, 2-arachidonoylglycerol (2-AG), which produces CB1 receptor-dependent reductions in inhibitory transmission, thereby increasing excitability of neurons which comprise output pathways responsible for cocaine seeking. Factors that influence the role of stress in cocaine seeking, including prior history of drug use, biological sex, chronic stress/co-morbid stress-related disorders, adolescence, social variables, and genetics are discussed.Better understanding when and how stress contributes to drug seeking should guide the development of more effective interventions, particularly for those whose drug use is stress related.

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Section: Role For Corticosteronesupporting

confidence: 87%

Neurochemical mechanisms and neurocircuitry underlying the contribution of stress to cocaine seeking

Caccamise

Newenhizen

Mantsch

2021

Journal of Neurochemistry

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“…We observed these cortisol measurements were positively associated with craving levels and negatively with the age of onset of drug consumption. Some studies about this topic have revealed that a deviation of cortisol secretion away from the homeostatic diurnal pattern in cocaine-dependent subjects was associated with reduced success at achieving early abstinence [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ]. This finding suggests a feed-forward cascade of effects of drugs on stress biology [ 58 ].…”

Section: Discussionmentioning

confidence: 99%

“…Regarding the association between morning cortisol levels and early age of onset, this could be related to a greater history of cocaine consumption [ 19 ]. Concerning this, some studies have demonstrated the influence of parental history of substance abuse on the risk of early drug abuse in their offspring [ 63 , 64 ], and for instance, higher morning cortisol levels have been found among crack cocaine users with positive family history and lower treatment retention [ 44 ]. Indeed, activation of the HPA response may be an early dysregulation associated with excessive and early drug taking that ultimately sensitizes the extrahypothalamic CRH systems [ 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , …”

Section: Discussionmentioning

confidence: 99%

“…Finally, this pilot experiment has several limitations that need to be considered and addressed in future studies. Regarding the sample, its size prevents the data from being generalizable and it would be also interesting to have collected data about treatment retention since recent studies have associated cortisol levels with this variable [ 44 ]. Moreover, although the main drug of consumption was cocaine, most of our subjects were poly-drug users, so we cannot totally rule out the effect of other substances, such as alcohol, on cognitive performance.…”

Section: Discussionmentioning

confidence: 99%

“…Finally, we have selected this type of sample collection because it has recently emerged as a reliable way of evaluating HPA function and it counts upon several advantages. For instance, its collection technique is non-invasive, inexpensive, easily obtainable and it has been shown to have a significant positive association with plasma cortisol [ 34 , 43 , 44 ].…”

Section: Introductionmentioning

confidence: 99%

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Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study

et al. 2020

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Cortisol is a glucocorticoid hormone secreted by the adrenal cortex upon the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Assessment of cortisol in saliva has emerged as a reliable way of evaluating HPA function. We examined the relationships between salivary cortisol levels with both craving and cognitive performance, as a possible biomarker of cocaine addiction. Cognitive performance (attention, declarative and working memory, executive functions and recognition of emotions) was assessed in 14 abstinent cocaine-dependent subjects in outpatient treatment and 13 control participants. Three salivary samples were collected at home by all the participants in the morning, afternoon and at bedtime. Patients showed higher levels of cortisol in the morning, as well as higher area under the curve with respect to the ground (AUCg). Regarding cognitive performance, cocaine-abstinent subjects showed worse performance in attention (d2 test), verbal memory (Spanish Complementary Verbal Learning Test, TAVEC) and executive tests (Tower of Hanoi and phonological fluency test) with respect to the control group. Morning cortisol levels and the AUCg index were negatively associated with the age of onset of drug consumption and the AUCg index was also positively associated with craving in our patients’ group. Moreover, morning cortisol levels, as well as the AUCg index, were negatively associated with verbal memory performance. Therefore, our pilot study suggests that salivary cortisol measurements could be a good avenue to predict craving level, as well as cognitive status, especially the declarative memory domain.

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Molecular pattern of a decrease in the rewarding effect of cocaine after an escalating-dose drug regimen

et al. 2022

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Background Long-term cocaine exposure leads to dysregulation of the reward system and initiates processes that ultimately weaken its rewarding effects. Here, we studied the influence of an escalating-dose cocaine regimen on drug-associated appetitive behavior after a withdrawal period, along with corresponding molecular changes in plasma and the prefrontal cortex (PFC). Methods We applied a 5 day escalating-dose cocaine regimen in rats. We assessed anxiety-like behavior at the beginning of the withdrawal period in the elevated plus maze (EPM) test. The reinforcement properties of cocaine were evaluated in the Conditioned Place Preference (CPP) test along with ultrasonic vocalization (USV) in the appetitive range in a drug-associated context. We assessed corticosterone, proopiomelanocortin (POMC), β-endorphin, CART 55–102 levels in plasma (by ELISA), along with mRNA levels for D2 dopaminergic receptor (D2R), κ-receptor (KOR), orexin 1 receptor (OX1R), CART 55–102, and potential markers of cocaine abuse: miRNA-124 and miRNA-137 levels in the PFC (by PCR). Results Rats subjected to the escalating-dose cocaine binge regimen spent less time in the cocaine-paired compartment, and presented a lower number of appetitive USV episodes. These changes were accompanied by a decrease in corticosterone and CART levels, an increase in POMC and β-endorphin levels in plasma, and an increase in the mRNA for D2R and miRNA-124 levels, but a decrease in the mRNA levels for KOR, OX1R, and CART 55–102 in the PFC. Conclusions The presented data reflect a part of a bigger picture of a multilevel interplay between neurotransmitter systems and neuromodulators underlying processes associated with cocaine abuse.

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Increased cortisol levels are associated with low treatment retention in crack cocaine users

Cited by 13 publications

References 45 publications

Neurochemical mechanisms and neurocircuitry underlying the contribution of stress to cocaine seeking

Neurochemical mechanisms and neurocircuitry underlying the contribution of stress to cocaine seeking

Salivary Cortisol Levels Are Associated with Craving and Cognitive Performance in Cocaine-Abstinent Subjects: A Pilot Study

Molecular pattern of a decrease in the rewarding effect of cocaine after an escalating-dose drug regimen

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