Drug withdrawal conceptualized as a stressor

Chartoff, Elena H.; Carlezon, William A.

doi:10.1097/fbp.0000000000000080

Cited by 34 publications

(22 citation statements)

References 315 publications

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“…Although there is little direct evidence linking sex differences in DYN and KOR systems to addictive behaviors, there is increasing evidence for sex differences in the role of KORs in mediating stress responses and affective states in preclinical animal models [184]. Given the importance of stress reactivity to addiction [22,38], this evidence may help us understand, on a mechanistic level, why addiction is experienced differently in men and women.…”

Section: Mu-opioid Receptorsmentioning

confidence: 99%

“…Below we provide a brief synopsis of the major neural circuits implicated in these stages of addiction, with a focus on opioids (mu-opioid receptor (MOR) agonists such as morphine, heroin, and oxycodone) and psychostimulants (e.g., cocaine, amphetamines). Comprehensive reviews are recommended for more in-depth coverage [15,[19][20][21][22][23].…”

Section: Introductionmentioning

confidence: 99%

“…Both mechanisms are thought to contribute to negative affective states observed during periods of drug withdrawal and abstinence. The homeostatic adaptations that occur in response to chronic drug exposure serve to oppose reward and, paradoxically, reinforce drug-seeking behavior [22,41,42].…”

Section: Introductionmentioning

confidence: 99%

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Sex differences in neural mechanisms mediating reward and addiction

Becker

Chartoff

2018

Neuropsychopharmacol

355

251

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There is increasing evidence in humans and laboratory animals for biologically based sex differences in every phase of drug addiction: acute reinforcing effects, transition from occasional to compulsive use, withdrawal-associated negative affective states, craving, and relapse. There is also evidence that many qualitative aspects of the addiction phases do not differ significantly between males and females, but one sex may be more likely to exhibit a trait than the other, resulting in population differences. The conceptual framework of this review is to focus on hormonal, chromosomal, and epigenetic organizational and contingent, sex-dependent mechanisms of four neural systems that are known-primarily in males-to be key players in addiction: dopamine, mu-opioid receptors (MOR), kappa opioid receptors (KOR), and brain-derived neurotrophic factor (BDNF). We highlight data demonstrating sex differences in development, expression, and function of these neural systems as they relate-directly or indirectly-to processes of reward and addictive behavior, with a focus on psychostimulants and opioids. We identify gaps in knowledge about how these neural systems interact with sex to influence addictive behavior, emphasizing throughout that the impact of sex can be highly nuanced and male/female data should be reported regardless of the outcome.

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Section: Mu-opioid Receptorsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sex differences in neural mechanisms mediating reward and addiction

Becker

Chartoff

2018

Neuropsychopharmacol

355

251

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“…Alcohol-withdrawal symptoms could be considered as a stressor factor since drug withdrawal leads to emotional and physical aversive states. These long-term effects might work as unpredictable and uncontrollable stressors, leading to a process of stress sensitization and enhancement of the endogenous aversive state due to drug withdrawal [78,79]. Thus, these subjects may not have good coping skills for facing the severity of withdrawal symptoms, leading to suicide attempts [77,80].…”

Section: Plos Onementioning

confidence: 99%

Prediction of attempted suicide in men and women with crack-cocaine use disorder in Brazil

et al. 2020

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Background Suicide is a severe health problem, with high rates in individuals with addiction. Considering the lack of studies exploring suicide predictors in this population, we aimed to investigate factors associated with attempted suicide in inpatients diagnosed with cocaine use disorder using two analytical approaches. Methods This is a cross-sectional study using a secondary database with 247 men and 442 women hospitalized for cocaine use disorder. Clinical assessment included the Addiction Severity Index, the Childhood Trauma Questionnaire, and the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, totalling 58 variables. Descriptive Poisson regression and predictive Random Forest algorithm were used complementarily to estimate prevalence ratios and to build prediction models, respectively. All analyses were stratified by gender. Results The prevalence of attempted suicide was 34% for men and 50% for women. In both genders, depression (PR M = 1.56, PR W = 1.27) and hallucinations (PR M = 1.80, PR W = 1.39) were factors associated with attempted suicide. Other specific factors were found for men and women, such as childhood trauma, aggression, and drug use severity. The men's predictive model had prediction statistics of AUC = 0.68, Acc. = 0.66, Sens. = 0.82, Spec. = 0.50, PPV = 0.47 and NPV = 0.84. This model identified several variables as important

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“…And the HPA axis is finely tuned by negative feedback from glucocorticoid, which activates glucocorticoid receptor within the paraventricular nucleus and the hippocampus ( Turnbull and Rivier, 1997 ). Acute psychostimulants exposure behaves like stressors that can elicit the activation of HPA axis ( Chartoff and Carlezon, 2014 ), and thus, induce the release of the above-mentioned molecules, which then exert immediate or delayed effects on the mesocorticolimbic system. However, acute withdrawal from chronic psychostimulants induces allosteric load in HPA axis, elevates secretion of CRF and ACTH, and decreases cortisol levels, which are hallmarks of depressive and anxiety spectrum disorders in man ( Li et al ., 2013a ; Zuloaga et al ., 2015 ).…”

Section: Relations Between Cart Containing Neural Circuits and Depresmentioning

confidence: 99%

Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression

Meng

Kim

et al. 2018

Biomol Ther (Seoul)

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Cocaine- and amphetamine-regulated transcript (CART) peptide is a widely distributed neurotransmitter expressed in the central nervous systems. Previously, several reports demonstrated that nucleus accumbal-injected CART peptide positively modulated behavioral sensitization induced by psychostimulants and regulated the mesocorticolimbic dopaminergic pathway. It is confirmed that CART peptide exerted inhibitory effect on psychostimulant-enhanced dopamine receptors signaling, Ca2+/calmodulin-dependent kinase signaling and crucial transcription factors expression. Besides modulation of dopamine receptors-related pathways, CART peptide also exhibited elaborated interactions with other neurotransmitter receptors, such as glutamate receptors and γ-aminobutyric acid receptors, which further account for attribution of CART peptide to inhibition of psychostimulant-potentiated locomotor activity. Recently, CART peptide has been shown to have anxiolytic functions on the aversive mood and uncontrolled drug-seeking behaviors following drug withdrawal. Moreover, microinjection of CART peptide has been shown to have an anti-depressant effect, which suggests its potential utility in the mood regulation and avoidance of depression-like behaviors. In this review, we discuss CART pathways in neural circuits and their interactions with neurotransmitters associated with psychostimulant-induced depression.

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Drug withdrawal conceptualized as a stressor

Cited by 34 publications

References 315 publications

Sex differences in neural mechanisms mediating reward and addiction

Sex differences in neural mechanisms mediating reward and addiction

Prediction of attempted suicide in men and women with crack-cocaine use disorder in Brazil

Cocaine- and Amphetamine-Regulated Transcript (CART) Peptide Plays Critical Role in Psychostimulant-Induced Depression

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