Reward Processing by the Opioid System in the Brain

University of Strasbourg, Strasburg, Alsace, France
Physiological Reviews (Impact Factor: 27.32). 10/2009; 89(4):1379-412. DOI: 10.1152/physrev.00005.2009
Source: PubMed


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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Available from: Julie Le Merrer
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    • "The same thing happens when a person suffers from a lack of social interaction (Le Merrer 2009). Activation of the endogenous opioid (and related neurohormonal) system forces him to undertake investigative and/or search activities: to seek what will replace for him the opioids received through social interaction. "
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    ABSTRACT: Domestication in essence represents a set of interactions of humans with other species, in which behavior has a leading role. At the same time, recent findings from neurochemical research highlight the importance of opioid system to such interactions. The combination of these neurochemical mechanisms and the peculiar social behavior of Neanderthal males could facilitate interactions between humans and wild species, and this type of behavior could be adopted by our ancestors in Eurasia from Neanderthals. These facilitative interactions could later lead to domestications. We propose that domestication is an artificial, social and personal system of the repeated use of results from the behavior and existence of specific representatives of animal and plant species, often obtained by means of genetic selection, with the initial aim of producing a greater amount of endogenous opioids and related neurohormones in the human organism. The new perspective can help generate empirically testable predictions. First, it predicts that interactions with plants, similar to interactions with animals, will launch cascades of neurochemical changes in the opioid system and establish certain patterns of our behavior; this prediction can be tested with the same experimental approach as used in the case of animals. Second, significant differences can be found in the ethnographic records on the interactions with animals between the shaman sub-cultures of Africa and Eurasia. Keywords: Domestication, Neanderthals, opioid system, pre-history, social behavior
    Full-text · Article · Dec 2015 · Kadmos
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    • "DYNORPHIN AND KAPPA OPIOID RECEPTORS (KORs) Dynorphins are a class of opioid peptides that arise from the precursor protein prodynorphin (pDYN) and act as endogenous ligands at the KOR (Chavkin and Goldstein, 1981). DYN and KORs are found throughout the central and peripheral nervous system (Mansour et al., 1988, 1995; Le Merrer et al., 2009), where they modulate a diverse set of physiological outputs including nociception, hypothermia, and water diuresis (Vonvoigtlander et al., 1983), as well as motivated behavior and affective states (Bruchas et al., 2010; Knoll and Carlezon, 2010). Protease cleavage of pDYN during processing releases multiple active peptides selective for the KOR including DYN A 1−8 & 1−17 , DYN B, and α/β-neoendorphins (Chavkin, 2013). "
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    ABSTRACT: Behavioral, biological, and social sequelae that lead to drug addiction differ between men and women. Our efforts to understand addiction on a mechanistic level must include studies in both males and females. Stress, anxiety, and depression are tightly linked to addiction, and whether they precede or result from compulsive drug use depends on many factors, including biological sex. The neuropeptide dynorphin (DYN), an endogenous ligand at kappa opioid receptors (KORs), is necessary for stress-induced aversive states and is upregulated in the brain after chronic exposure to drugs of abuse. KOR agonists produce signs of anxiety, fear, and depression in laboratory animals and humans, findings that have led to the hypothesis that drug withdrawal-induced DYN release is instrumental in negative reinforcement processes that drive addiction. However, these studies were almost exclusively conducted in males. Only recently is evidence available that there are sex differences in the effects of KOR activation on affective state. This review focuses on sex differences in DYN and KOR systems and how these might contribute to sex differences in addictive behavior. Much of what is known about how biological sex influences KOR systems is from research on pain systems. The basic molecular and genetic mechanisms that have been discovered to underlie sex differences in KOR function in pain systems may apply to sex differences in KOR function in reward systems. Our goals are to discuss the current state of knowledge on how biological sex contributes to KOR function in the context of pain, mood, and addiction and to explore potential mechanisms for sex differences in KOR function. We will highlight evidence that the function of DYN-KOR systems is influenced in a sex-dependent manner by: polymorphisms in the prodynorphin (pDYN) gene, genetic linkage with the melanocortin-1 receptor (MC1R), heterodimerization of KORs and mu opioid receptors (MORs), and gonadal hormones. Finally, we identify several gaps in our understanding of “if” and “how” DYN and KORs modulate addictive behavior in a sex-dependent manner. Future work may address these gaps by building on the mechanistic studies outlined in this review. Ultimately this will enable the development of novel and effective addiction treatments tailored to either males or females.
    Full-text · Article · Dec 2015 · Frontiers in Neuroscience
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    • "In these studies manipulating the opioid system, the expected outcome (i.e., the predicted pain signal) did not match the actual outcome (i.e., the actually perceived nociceptive stimulus) – which describes exactly the discrepancy between expected and received outcomes as reflected by prediction error signals. Although previous research assumed that endogenous opioids are primarily involved in nociception and analgesia, but also in hedonic control and reward processing (Le Merrer, et al., 2009), the mentioned Contents lists available at ScienceDirect journal homepage: Neuropsychologia 0028-3932/& 2015 The Authors. "
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    ABSTRACT: Recent research suggests that not only the dopamine neurotransmitter system but also the endogenous opioid system is involved in performance monitoring and the generation of prediction error signals. Therefore, the current study investigated the potential link between the functional opioid peptide prodynorphin (PDYN) 68bp VNTR genetic polymorphism and neuronal correlates of performance monitoring. To this end, forty-seven healthy participants genotyped for this polymorphism, related to high-, intermediate-, and low-expression levels of PDYN, performed a choice-reaction task while their electroencephalogram (EEG) was recorded. On the ehavioural level, no differences between the three PDYN groups could be observed. EEG data, however, showed significant differences. High PDYN expression individuals showed heightened neural error processing indicated by higher ERN amplitudes, compared to intermediate and low expression individuals. Later stages of error processing, indexed by late Pe amplitudes, and stimulus-driven conflict processing, indexed by N2 amplitudes, were not affected by PDYN genotype. The current results corroborate the notion of an indirect effect of endogenous opioids on performance monitoring, probably mediated by the mesencephalic dopamine system. Overall, enhanced ERN amplitudes suggest a hyper-active performance monitoring system in high PDYN expression individuals, and this might also be an indicator of a higher risk for internalizing disorders. Copyright © 2015. Published by Elsevier Ltd.
    Full-text · Article · Sep 2015 · Neuropsychologia
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