Acute Effects of Heroin on Negative Emotional Processing: Relation of Amygdala Activity and Stress-Related Responses

Schmidt, André; Borgwardt, Stefan; Gerber, Helmut; Wiesbeck, Gerhard A.; Schmid, Otto; Riecher-Rössler, Anita; Smieskova, Renata; Lang, Undine E.; Walter, Marc

doi:10.1016/j.biopsych.2013.10.019

Cited by 110 publications

(73 citation statements)

References 49 publications

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“…Cocaine craving is enhanced in cocaine seekers by D-cycloserine (507). There are similarities between craving behavior for different drugs, but the relation between the effects of D-cycloserine and those of pexacerfont, if any, is not even hinted at; the relation of both to fear learning is not known, although of course there is a strong component of anxiety and even fear in drug-deprived addicts (583,584). The neurokinin-1 antagonist aprepitant activates the vmPFC, an area critical both for learning (see sect.…”

Section: Corticotropin-releasing Factormentioning

confidence: 99%

Fear Memory

Izquierdo

Furini

Myskiw

2016

Physiological Reviews

363

259

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Fear memory is the best-studied form of memory. It was thoroughly investigated in the past 60 years mostly using two classical conditioning procedures (contextual fear conditioning and fear conditioning to a tone) and one instrumental procedure (one-trial inhibitory avoidance). Fear memory is formed in the hippocampus (contextual conditioning and inhibitory avoidance), in the basolateral amygdala (inhibitory avoidance), and in the lateral amygdala (conditioning to a tone). The circuitry involves, in addition, the pre-and infralimbic ventromedial prefrontal cortex, the central amygdala subnuclei, and the dentate gyrus. Fear learning models, notably inhibitory avoidance, have also been very useful for the analysis of the biochemical mechanisms of memory consolidation as a whole. These studies have capitalized on in vitro observations on long-term potentiation and other kinds of plasticity. The effect of a very large number of drugs on fear learning has been intensively studied, often as a prelude to the investigation of effects on anxiety. The extinction of fear learning involves to an extent a reversal of the flow of information in the mentioned structures and is used in the therapy of posttraumatic stress disorder and fear memories in general.

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Section: Corticotropin-releasing Factormentioning

confidence: 99%

Fear Memory

Izquierdo

Furini

Myskiw

2016

Physiological Reviews

363

259

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“…Our recent functional magnetic resonance induction (fMRI) studies using emotionally stimulating pictures during measurement also demonstrated decreased activation in the amygdala after the administration of DAM compared to saline. This decreased amygdala activation is associated with decreases in stress hormone levels and negative emotions in patients with stable DAM-assisted treatment [2]. Furthermore, we could show a direct relation between acute heroin effects on stress-related emotions, stress reactivity, and the left amygdala response to negative facial expressions [2].…”

Section: Introductionmentioning

confidence: 98%

“…This decreased amygdala activation is associated with decreases in stress hormone levels and negative emotions in patients with stable DAM-assisted treatment [2]. Furthermore, we could show a direct relation between acute heroin effects on stress-related emotions, stress reactivity, and the left amygdala response to negative facial expressions [2]. …”

Section: Introductionmentioning

confidence: 98%

“…L-Methadone, buprenorphine, and diacetylmorphine or diamorphine (DAM) produce favorable treatment retention and outcome in opioid and heroin dependence. Substitution predictably resolves craving-induced stress and anxiety, making the individual compliant to other forms of therapy [2]. In previous reports, DAM-assisted treatment was consistently found to be an effective treatment for severe heroin dependence [3-5].…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of POMC and NR3C1

Groh¹,

Rhein²,

Buchholz³

et al. 2017

Neuropsychobiology

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The administration of diacetylmorphine (DAM) reduces the activation of the hypothalamic-pituitary-adrenal (HPA) axis in opioid-maintained patients. However, the epigenetic effects of DAM on addiction-related genes have not been investigated yet. In a randomized controlled study, we examined the immediate effects of intravenous DAM versus placebo on the promoter methylation of the POMC (pro- opiomelanocortin) and NR3C1 (glucocorticoid receptor 1) genes. Twenty-eight heroin-dependent patients on DAM-assisted treatment received either DAM or saline in a randomized crossover design and 17 healthy participants received saline only. EDTA blood samples were taken 25 min before and 10 min after the injection of DAM or saline. We found reciprocal regulation effects for DAM versus saline application regarding the methylation of POMC; while DAM injection significantly increased methylation, saline injection led to a significant decrease in methylation for patients as well as controls. NR3C1 data did not show significant changes in methylation. Injection of DAM blunted stress hormone levels and the POMC promoter methylation of heroin-dependent patients. These findings provide first preliminary insights into the epigenetic mechanisms underlying the emotional regulation effects of DAM-assisted treatment in severe heroin-dependent patients.

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“…These patients show elevated stress reactivity during withdrawal syndrome, which is related to heightened craving and symptoms of withdrawal [12]. Indeed, the activation of the hypothalamic-pituitary-adrenocortical axis and the elevated cortisol levels have been reported during opioid withdrawal syndromes, while opioid agonist administration reduced cortisol secretion, craving scores and amygdala activity in heroindependent patients [13]. Furthermore, dehydroepiandrosterone sulphate (DHEAS) may buffer the effects of cortisol and play a role in the resilience and in successful adaptation to the stress.…”

Section: Introductionmentioning

confidence: 99%

The Effects of Oxytocin on Withdrawal, Craving and Stress Response in Heroin-Dependent Patients: A Randomized, Double-Blind Clinical Trial

et al. 2019

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Opioid dependence is an increasing clinical and public health problem. Current pharmacotherapies have limited efficacy and cause serious side effects. Increasing bodies of evidences suggest the neuropeptide, oxytocin (OT), as a potential treatment for drug abuse disorders. The current study was designed to evaluate the effect of OT on withdrawal, craving and anxiety scores, cortisol and dehydroepiandrosterone sulphate (DHEAS) blood level in heroin-dependent male patients. This randomized, double-blind placebo-controlled clinical trial was conducted on 58 males with opioid dependence by Abstinence Center of Addictive People in Iran. The participants were randomly allocated to receive intranasal OT (single dose; 40 IU, n = 29) or placebo (n = 29). Heroine withdrawal, craving and anxiety scores were measured using the Opioid Withdrawal Scale, Visual Analogue Scale and (Desire for Drug Questionnaire), and Hamilton checklist respectively. The cortisol and DHEAS levels at baseline and different post-intervention time were measured using a competitive immunoanalysis method. Acute OT administration reduced craving and withdrawal scores but did not change anxiety significantly. Single dose of OT decreased the level of cortisol and improved the cortisol/DHEAS ratio in the heroin users during abstinence (p < 0.01). These results suggest that OT may be useful in the attenuation of craving, withdrawal symptom in heroin-dependent patients and might be considered a new potential treatment for heroin dependence where positive effects of OT on stress-related hormones may be involved in this effect of OT.

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Acute Effects of Heroin on Negative Emotional Processing: Relation of Amygdala Activity and Stress-Related Responses

Cited by 110 publications

References 49 publications

Fear Memory

Fear Memory

Epigenetic Effects of Intravenous Diacetylmorphine on the Methylation of <b><i>POMC</i></b> and <b><i>NR3C1</i></b>

The Effects of Oxytocin on Withdrawal, Craving and Stress Response in Heroin-Dependent Patients: A Randomized, Double-Blind Clinical Trial

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