Reward Processing by the Opioid System in the Brain

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous opioid peptides processed from three protein precursors, proopiomelanocortin, proenkephalin, and prodynorphin. Opioid receptors are recruited in response to natural rewarding stimuli and drugs of abuse, and both endogenous opioids and their receptors are modified as addiction develops. Mechanisms whereby aberrant activation and modifications of the opioid system contribute to drug craving and relapse remain to be clarified. This review summarizes our present knowledge on brain sites where the endogenous opioid system controls hedonic responses and is modified in response to drugs of abuse in the rodent brain. We review 1) the latest data on the anatomy of the opioid system, 2) the consequences of local intracerebral pharmacological manipulation of the opioid system on reinforced behaviors, 3) the consequences of gene knockout on reinforced behaviors and drug dependence, and 4) the consequences of chronic exposure to drugs of abuse on expression levels of opioid system genes. Future studies will establish key molecular actors of the system and neural sites where opioid peptides and receptors contribute to the onset of addictive disorders. Combined with data from human and nonhuman primate (not reviewed here), research in this extremely active field has implications both for our understanding of the biology of addiction and for therapeutic interventions to treat the disorder.

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Opioid peptides and testicular activity in the lizard Podarcis s. sicula Raf

Journal of Endocrinology ◽

10.1677/joe.0.1430565 ◽

1994 ◽

Vol 143 (3) ◽

pp. 565-571 ◽

Cited By ~ 15

Author(s):

G Ciarcia ◽

F Facchinetti ◽

M Vallarino ◽

M Pestarino ◽

M Paolucci ◽

...

Keyword(s):

Opioid Peptides ◽

High Performance ◽

Physiological Role ◽

Reproductive Activity ◽

Opioid System ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Naltrexone Treatment

Abstract In mammals endorphinergic systems have been shown to modulate reproductive processes and β-endorphin (β-EP) has been found to influence sexual functions, acting at the hypothalamus-pituitary-gonadal axis level. Using immunocytochemical and in vitro studies, evidence for a diffuse pro-opiomelanocortin-related opioid system in the lizard Podarcis s. sicula was produced. In the testis, β-EP immunoreactivity showed seasonal variation, being most pronounced in the interstitial cells of sexually quiescent lizards (December). Reverse-phase high-performance liquid chromatography, coupled with radioimmunoassay and immunocytochemistry, showed that β-EP and acetyl β-EP increased during December, while their concentrations were low during April, when the highest testicular activity occurred. Using in vivo studies, it was found that naltrexone treatment, blocking pituitary opioid receptor, increased androgen levels in the plasma and in the testis. It was also found with in vitro studies that the endogenous opioid system inhibits gonadotrophin release and therefore androgen production by the testis. The data reported here provide evidence for the physiological role played by opioid peptides at the pituitary level to regulate the seasonal reproductive activity of the lizard Podarcis s. sicula. Journal of Endocrinology (1994) 143, 565–571

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ENDOGENOUS OPIOID SYSTEM AS A MEDIATOR OF ACUTE AND LONG-TERM ADAPTATION TO STRESS. PROSPECTS FOR CLINICAL USE OF OPIOID PEPTIDES

Annals of the Russian academy of medical sciences ◽

10.15690/vramn.v67i6.287 ◽

2012 ◽

Vol 67 (6) ◽

pp. 73-82 ◽

Cited By ~ 6

Author(s):

Yu. B. Lishmanov ◽

L. N. Maslov ◽

N. Yu. Naryzhnaya ◽

J.-M. Pei ◽

F. Kolar ◽

...

Keyword(s):

Opioid Peptides ◽

Ischemia Reperfusion ◽

Antiarrhythmic Effect ◽

Endogenous Opioids ◽

Protective Effects ◽

Adaptive Responses ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Future Clinical Practice ◽

Thromboxane Production

It has been well established that opioid peptides (OPs) affect various hormonal systems. Opioids exhibit stress-limiting and gastro-protective effects in stressed animals, acting via μ- and δ-opioid receptors (OR). Peripheral μ-OR stimulation by endogenous and exogenous opioids increases cardiac tolerance to pathological consequences of stress. Enhancement of prostacyclin synthesis, decrease of thromboxane production as well as suppression of lipid peroxidation can be directly responsible for cardioprotective effects of OPs in stressed animals. Adaptive responses are accompanied by increased OP levels in blood and tissues. Reduction of ventricular arrhythmias induced by repeated short-term immobilization stress is mediated via μ-OR stimulation by endogenous opioids, while δ-OR account for an antiarrhythmic effect of adaptation to chronic intermittent hypobaric hypoxia. The mechanism of infarct size-limiting effect of continuous normobaric hypoxia involves both μ- and δ-OR stimulation. Peptide OR agonists can be considered in future clinical practice for treatment of withdrawal syndrome, stress-related cardiac disease or myocardial injury caused by ischemia-reperfusion insult.

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Formation of fetal opioid system

Journal of obstetrics and women s diseases ◽

10.17816/jowd65264-69 ◽

2016 ◽

Vol 65 (2) ◽

pp. 64-69 ◽

Cited By ~ 1

Author(s):

Anastasia A Yakovleva

Keyword(s):

Growth Hormone ◽

Opioid Peptides ◽

Opioid System ◽

Endogenous Opioid Peptides ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Placental Lactogens ◽

Functional Development ◽

The Central Nervous System ◽

Different Tissues

The article presented literature review about of endogenous opioid system (EOS) formation consist of opioid receptors complex and its ligands (endogenous opioid peptides) in different tissues including placenta. It was shown that formation of fetal EOS is going with anatomic and functional development of the central nervous system and EOS expression begins in the placental tissues as soon as implantation and starts till the end of the pregnancy. Influence of opioid peptides on secretion progesterone, prolactin family peptides, growth hormone, placental lactogens and prolypherine from the trophoblast tissue is discussed.

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Endogenous Opioids at the Intersection of Opioid Addiction, Pain, and Depression: The Search for a Precision Medicine Approach

Annual Review of Neuroscience ◽

10.1146/annurev-neuro-110719-095912 ◽

2020 ◽

Vol 43 (1) ◽

pp. 355-374

Author(s):

Michael A. Emery ◽

Huda Akil

Keyword(s):

Individual Differences ◽

Mood Disorders ◽

Sensation Seeking ◽

The United States ◽

Opioid Addiction ◽

Endogenous Opioids ◽

Opioid Abuse ◽

Opioid System ◽

Endogenous Opioid System ◽

Endogenous Opioid

Opioid addiction and overdose are at record levels in the United States. This is driven, in part, by their widespread prescription for the treatment of pain, which also increased opportunity for diversion by sensation-seeking users. Despite considerable research on the neurobiology of addiction, treatment options for opioid abuse remain limited. Mood disorders, particularly depression, are often comorbid with both pain disorders and opioid abuse. The endogenous opioid system, a complex neuromodulatory system, sits at the neurobiological convergence point of these three comorbid disease states. We review evidence for dysregulation of the endogenous opioid system as a mechanism for the development of opioid addiction and/or mood disorder. Specifically, individual differences in opioid system function may underlie differences in vulnerability to opioid addiction and mood disorders. We also review novel research, which promises to provide more detailed understanding of individual differences in endogenous opioid neurobiology and its contribution to opioid addiction susceptibility.

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Borderline personality disorder - a dysregulation of the endogenous opioid system?

European Psychiatry ◽

10.1016/s0924-9338(11)72713-4 ◽

2011 ◽

Vol 26 (S2) ◽

pp. 1008-1008

Author(s):

B. Bandelow ◽

C. Schmahl ◽

P. Falkai ◽

D. Wedekind

Keyword(s):

Borderline Personality Disorder ◽

Personality Disorder ◽

Opioid Receptors ◽

Borderline Personality ◽

Endogenous Opioids ◽

The Body ◽

Opioid System ◽

Endogenous Opioid System ◽

Endogenous Opioid ◽

Self Injury

The neurobiology of borderline personality disorder (BPD) remains unclear. Dysfunctions of several neurobiological systems have been discussed, including serotoninergic, dopaminergic, and other neurotransmitter systems.Here we present a theory that alterations in the sensitivity of opioid receptors or the availability of endogenous opioids constitute part of the underlying pathophysiology of BPD.1 The alarming symptoms and self-destructive behaviors of the affected patients may be explained by uncontrollable and unconscious attempts to stimulate their endogenous opioid system (EOS) and the dopaminergic reward system, regardless of the possible harmful consequences. Neurobiological findings that support this hypothesis are reviewed: Frantic efforts to avoid abandonment, frequent and risky sexual contacts, and attention-seeking behavior may be explained by attempts to make use of the rewarding effects of human attachment mediated by the EOS. Anhedonia and feelings of emptiness may be an expression of reduced activity of the EOS. Patients with BPD tend to abuse substances that target μ-opioid receptors. Self-injury, food-restriction, aggressive behavior, and sensation-seeking may be interpreted as a desperate attempt to artificially set the body to “survival mode”, in order to mobilize the last reserves of the EOS. BPD-associated symptoms, such as substance abuse, anorexia, self-injury, depersonalization, and sexual overstimulation, can be treated successfully with μ-opioid receptor antagonists.An understanding of the neurobiology of BPD may help in developing new treatments for patients with this severe disorder.

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