Siri Leknes

University of Oslo · Department of Psychology

Social mammals engage in affiliative interactions both when seeking relief from negative affect and when searching for pleasure and joy. These two motivational states are both modulated by μ-opioid transmission. The μ-opioid receptor (MOR) system in the brain mediates pain relief and reward behaviors, and is implicated in social reward processing a...

Pain is mostly thought of as a problem-as debilitating or harmful. Despite its unpleasantness, however, under some conditions pain can be associated with positive consequences. In this review, we explore these positive biological, psychological, and social consequences of pain. We highlight three different domains in which pain may be considered to...

Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment

Interpersonal touch is frequently used for communicating emotions, strengthen social bonds and to give others pleasure. The neuropeptide oxytocin increases social interest, improves recognition of others’ emotions, and it is released during touch. Here, we investigated how oxytocin and gentle human touch affect social impressions of others, and vic...

Significance Placebo effects illustrate the power of the human brain; simply expecting an improvement can alter pain processing and produce analgesia. We induced placebo improvement of both negative and positive feelings (painful and pleasant touch) in healthy humans, and compared the brain processing using functional MRI. Pain reduction dampened s...

Social bonding, essential for health and survival in all social species, depends on mu-opioid signalling in non-human mammals. A growing neuroimaging and psychopharmacology literature also implicates mu-opioids in human social connectedness. To determine the role of mu-opioids for social connectedness in healthy humans, we conducted a preregistered...

Maladaptive stress responses may exacerbate chronic widespread pain (CWP) and deserve further investigations. Yet, existing paradigms lack relevance for individuals with this condition. Hence, we developed the Social Benefits Stress Test (SBST), adapted from the Trier Social Stress Test. Instead of a job interview, the patients’ task is to justify...

Rationale Anabolic-androgenic steroids (AAS) are used to improve physical performance and appearance, but have been associated with deficits in social cognitive functioning. Approximately 30% of people who use AAS develop a dependence, increasing the risk for undesired effects. Objectives To assess the relationship between AAS use (current/previou...

Men are disproportionately likely to develop opioid use disorder, yet the mechanisms of addiction risk in men and women remain poorly understood. Preclinical, epidemiological and clinical studies converge upon stress as a key risk factor. To determine the mechanisms through which stress alters abuse liability, we measured opioid self-administration...

Background: Opioid exposure after surgery increases risk of persistent opioid use. Here, we characterize at-home use of opioid rescue medication during 1-2 days after outpatient surgery (N=270) in a postoperative opioid-sparing context at a Norwegian hospital. Methods: The postsurgical pain management plan included non-steroidal anti-inflammator...

Exposure to opioid analgesics due to surgery increases the risk of new persistent opioid use. A mechanistic hypothesis for opioids' abuse liability rests on the belief that, in addition to pain relief, acute opioid treatment improves well-being (e.g. via euphoria) and relieves anxiety. However, opioids do not consistently improve mood in laboratory...

Background: Anabolic-androgenic steroids (AAS) are used to improve physical performance and to achieve a muscular appearance, with significant physical and psychiatric consequences. Approximately 30% of people who use AAS develop a dependence, increasing the risk for undesired effects, largely driven by endocrine dysfunction. AAS use has been assoc...

People in economically advantaged nations tend to evaluate their life as more positive overall and report greater well-being than people in less advantaged nations. But how does positivity manifest in the daily life experiences of individuals around the world? The present study asked 15,244 college students from 62 nations, in 42 languages, to desc...

How does social support bolster resilience? Here, we present a new dyadic paradigm to study causal mechanisms of acute and ecologically valid social support in the laboratory. The Dyadic Stress and Support Task (DSST) consists of a psychosocial stress phase and a recovery phase. During DSST stress, a pair of participants take turns to perform publi...

Opioid exposure after surgery increases risk of persistent opioid use. Here, we characterize at-home use of opioid rescue medication during acute recovery after day surgery (N=270) in an opioid sparing context. The post-surgical pain management plan included non-steroidal anti-inflammatory drugs and up to 6 pills of 5mg oxycodone to be taken as nee...

Non-human animal studies outline precise mechanisms of central mu-opioid regulation of pain, stress, affiliation and reward processing. In humans, pharmacological blockade with non-selective opioid antagonists such as naloxone and naltrexone is typically used to assess involvement of the mu-opioid system in such processing. However, robust estimate...

Exposure to opioid analgesics due to surgery increases the risk of new persistent opioid use. A mechanistic hypothesis for opioids’ abuse liability rests on the belief that in addition to pain relief, acute opioid treatment improves mood, e.g. via euphoria and anxiety relief. However, opioids do not consistently improve mood in laboratory studies o...

How does social support bolster resilience? Here, we present a new dyadic paradigm to study causal mechanisms of acute and ecologically valid social support in the laboratory. The Dyadic Stress and Support Task (DSST) consists of a psychosocial stress phase and a recovery phase. During DSST stress, a pair of participants take turns to perform publi...

Background There are currently no approved medications for impaired social cognition and function, core symptoms of autism spectrum disorder. We describe marked improvement of these symptoms with long-term low-dose administration of the partial µ-opioid agonist buprenorphine. We discuss these observations in the context of a role for endogenous opi...

The pleasantness of gentle stroking (CT-targeted touch) varies highly between individuals and studies, indicating that relevant factors may not be accounted for. We propose that the affective value of a touch event is determined by how well its perceived purpose matches the goals of the touch receiver. The perceived purpose or meaning of touch is i...

Non-human animal studies outline precise mechanisms of central mu-opioid regulation of pain, stress, affiliation and reward processing. In humans, pharmacological blockade with non-selective opioid antagonists such as naloxone and naltrexone is typically used to assess involvement of the mu-opioid system in such processing. However, robust estimate...

Oxytocin is central to pair-bonding in non-human animals. We assessed effects of intranasal oxytocin on bond formation between two opposite-sex strangers. In a double-blind placebo-controlled design, 50 pairs of one man and one woman received oxytocin or placebo spray intranasally. After treatment, they played a social interaction game, followed by...

We discuss how effects of different magnitudes from human opioid antagonist studies can be interpreted and how the results inform us on the role of the endogenous mu-opioid system for pain relief and other affective processes in humans. This is a commentary on Endogenous opioids contribute to the feeling of pain relief in humans by Sirucek et al, I...

Purpose of Review Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation and anhedonia, have been linked to endogenous opioid signalling. Whereas chronic substance use and misuse are thought to alter the function of the...

The endogenous opioid system has been implicated during experiences of pleasure (i.e., from food or sex). Music can elicit intense emotional and bodily sensations of pleasure, called ‘Chills’. We investigated the effects of an opioid antagonist (50 mg naltrexone) or placebo (40 μg d3-vitamin) while listening to self-selected music or other ‘control...

Purpose of review. Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation & anhedonia, have been linked to endogenous opioid signaling. Whereas chronic substance use and misuse are thought to alter the function of the m...

The brain systems underlying placebo analgesia are insufficiently understood. Here we performed a systematic, participant-level meta-analysis of experimental functional neuroimaging studies of evoked pain under stimulus-intensity-matched placebo and control conditions, encompassing 603 healthy participants from 20 (out of 28 eligible) studies. We f...

Abstract What does it mean to be happy? The vast majority of cross-cultural studies on happiness have employed a Western-origin, or “WEIRD” measure of happiness that conceptualizes it as a self-centered (or “independent”), high-arousal emotion. However, research from East�ern cultures, particularly Japan, conceptualizes happiness as including an in...

Dilating the pupils allow more quanta of light to impact the retina. Consequently, if one pupil is dilated with a pharmacological agent (Tropicamide), the brightness of a surface under observation should increase pro- portionally to the pupil dilation. Little is known about causal effects of changes in pupil size on perception of an object’s bright...

The mechanisms underlying the role of oxytocin (OT) as a regulator of social behavior in mammals are only partly understood. Recently, it has been proposed that OT increases the salience of social stimuli. We carried out a randomized, double-blind, cross-over study of the effects of OT on binocular rivalry, a visual phenomenon underpinned by the in...

Importance Anhedonia, a reduced capacity for pleasure, is described for many psychiatric and neurologic conditions. However, a decade after the Research Domain Criteria launch, whether anhedonia severity differs between diagnoses is still unclear. Reference values for hedonic capacity in healthy humans are also needed. Objective To generate and co...

Objective The current exploratory study sought to examine dispositional optimism, or the general expectation for positive outcomes, around the world. Method Dispositional optimism and possible correlates were assessed across 61 countries (N = 15,185; mean age = 21.92; 77% female). Mean‐level differences in optimism were computed along with their r...

Pathogens represent a significant threat to human health leading to the emergence of strategies designed to help manage their negative impact. We examined how spiritual beliefs developed to explain and predict the devastating effects of pathogens and spread of infectious disease. Analysis of existing data in studies 1 and 2 suggests that moral vita...

Rationale Illicit use of anabolic androgenic steroids (AAS) has grown into a serious public health concern throughout the Western World. AAS use is associated with adverse medical, psychological, and social consequences. Around 30% of AAS users develop a dependence syndrome with sustained use despite adverse side effects. AAS dependence is associat...

Background Both acute and chronic pain can disrupt reward processing. Moreover, prolonged prescription opioid use and depressed mood are common in chronic pain samples. Despite the prevalence of these risk factors for anhedonia, little is known about anhedonia in chronic pain populations. Methods We conducted a large-scale, systematic study of anh...

The μ-opioid receptor (MOR) system has long been thought to underpin the rewarding properties of pleasant touch. Numerous non-human animal studies implicate MORs in social behaviours involving touch, but little is currently known about MOR involvement in human touch reward. Here, we employed a bi-directional pharmacological double-blind crossover d...

The opioid system regulates affective processing, including pain, pleasure, and reward. Restricting the role of this system to hedonic modulation may be an underestimation, however. Opioid receptors are distributed widely in the human brain, including the more “cognitive” regions in the frontal and parietal lobes. Nonhuman animal research points to...

Disruption of non-drug reward processing in addiction could stem from long-term drug use, addiction-related psychosocial stress, or a combination of these. It remains unclear whether long-term opioid maintenance treatment (OMT) disrupts reward processing. Here, we measured subjective and objective reward responsiveness in 26 previously heroin-addic...

Both acute and chronic pain can disrupt reward processing. Moreover, prolonged prescription opioid use and depressed mood are common in chronic pain samples. Despite the prevalence of these risk factors for anhedonia, little is known about the capacity for pleasure in chronic pain populations. We investigated anhedonia in chronic pain patients and...

The mu-opioid receptor (MOR) system has long been thought to underpin the rewarding properties of pleasant touch. Numerous non-human animal studies implicate MORs in social behaviours involving touch, but little is currently known about MOR involvement in human touch reward. Here, we employed a bi-directional pharmacological double-blind crossover...

Background. Drug dependence is associated with disrupted reward processing and anhedonia across drug use disorders. It remains unclear whether chronic drug use disrupts reward processing. Alternative causes could be psychosocial vulnerability factors or stress from recurring relapse to drug use. Methods. We measured subjective and objective reward...

Caress-like touch is thought to rely on C-tactile (CT) fiber signaling. Here, the arousing and emotional effects of CT-optimal touch were assessed via participants' skin conductance level (SCL), facial electromyography (EMG) responses and subjective ratings of pleasantness and intensity. Temporal facial EMG analysis was based on the conduction velo...

Pain is regulated endogenously through both opioid and non-opioid mechanisms. We hypothesized that two novel pain modulation tasks, one drawing on context/expectations and one using voluntary reappraisal, would show differing levels of opioid dependence. Specifically, we expected that naloxone would block context-related analgesia, whereas mental i...

The opioid system plays a key role in the regulation of affective processing including pain, pleasure, and reward. However, there is also increasing evidence that this system plays a broader role and can modulate cognitive function. In particular, increasing evidence suggests that the mu-opioid system influences how we choose between actions of dif...

The opioid system plays a key role in the regulation of affective processing including pain, pleasure, and reward. However, there is also increasing evidence that this system plays a broader role and can modulate cognitive function. In particular, increasing evidence suggests that the mu-opioid system influences how we choose between actions of dif...

The μ-opioid system modulates responses to pain and psychosocial stress and mediates non-social and social reward. In humans, the μ-opioid agonist morphine can increase overt attention to the eye-region and visual exploration of faces with neutral expressions. However, little is known about how the human μ-opioid system influences sensitivity to an...

Modifying behavior to maximize reward is integral to adaptive decision making. In rodents, the μ-opioid receptor (MOR) system encodes motivation and preference for high-value rewards. Yet it remains unclear whether and how human MORs contribute to value-based decision making. We reasoned that if the human MOR system modulates value-based choice, th...

Background: C-tactile (CT) afferents are unmyelinated low-threshold mechanoreceptors optimized for signalling affective, gentle touch. In three separate psychophysical experiments, we examined the contribution of CT afferents to pain modulation. Methods: In total, 44 healthy volunteers experienced heat pain and CT optimal (slow brushing) and CT...

Affiliative touch interactions are often rewarding. They can on one hand alleviate stress and negative affect, while on the other hand induce intense feelings of pleasure. The behavioral nature of touch interactions (e.g., soothing soft touch or rough-and-tumble play) is often very different depending on whether the motivation for touch is primaril...

Background Rodent models highlight the key role of μ-opioid receptor (MOR) signaling in palatable food consumption. In humans, however, the effects of MOR stimulation on eating and food liking remain unclear. Objectives Here, we tested sweet pleasantness experience in humans following MOR drug manipulations. We hypothesized that behaviors regulated...

The neuropeptide oxytocin (OT) is associated with a plethora of social behaviors, and is a key topic at the intersection of psychology and biology. However, tools for measuring OT are still not fully developed. We describe a robust nano liquid chromatography-mass spectrometry (nanoLC-MS) platform for measuring the total amount of OT in human plasma...

Paying attention to others’ faces and eyes is a cornerstone of human social behavior. The µ-opioid receptor (MOR) system, central to social reward-processing in rodents and primates, has been proposed to mediate the capacity for affiliative reward in humans. We assessed the role of the human MOR system in visual exploration of faces and eyes of con...

Most studies of neuro-functional patterns in trauma-exposed individuals have been conducted considerable time after the traumatic event. Hence little is known about neuro-functional processing shortly after trauma-exposure. We investigated brain activity patterns in response to trauma reminders as well as neutral and negative stimuli in individuals...

Current approaches to measuring the cyclic peptide oxytocin in plasma/serum are associated with poor selectivity and/or inadequate sensitivity. We here describe a high performance nano liquid chromatography-mass spectrometry platform for measuring OT in human plasma/serum. The platform is extremely robust, allowing laborious sample clean-up steps t...

Inter-individual touch can be a desirable reward that can both relieve negative affect and evoke strong feelings of pleasure. However, if other sensory cues indicate it is undesirable to interact with the toucher, the affective experience of the same touch may be flipped to disgust. While a broad literature has addressed, on one hand the neurophysi...

The hedonic processing of pleasure, pain, and displeasure is essential to survival and as such motivates behavior and strongly influences decision-making. Research has shown that the underlying mechanisms of wanting, liking, and learning form partly separable neuroanatomical and neuropharmacological systems in the brain, which are shared among many...

Neurons communicate via chemical signals called neurotransmitters (NTs). The numerous identified NTs can have very different physiochemical properties (solubility, charge, size etc.), so quantification of the various NT classes traditionally requires several analytical platforms/methodologies. We here report that a diverse range of NTs, e.g. peptid...

Supplementary information

Background: Early neurocognitive changes in emotional processing are seen following SSRI administration, which may be involved in mechanisms of action. However, the perceptual processes underpinning these effects have not been specified. Methods: In a double-blind, placebo-controlled eye-tracking study, we assessed the effect of single dose of c...

Pain is most often an unpleasant experience that alerts us to actual or possible tissue damage. However, insisting that pain is always bad news may hinder understanding of pain’s many facets. Despite its unpleasantness – or perhaps because of it – pain is known to enhance the perceived value of certain activities, such as punishment or endurance sp...

The sensory systems of touch and pain provide us with information about our environment and our bodies that is often crucial for survival and well-being. Moreover, touch is a source of pleasure. In this chapter, we review how information about our environment and our bodies is coded in the periphery and interpreted by the brain as touch and pain se...

Context can influence the experience of any event. For instance, the thought that "it could be worse" can improve feelings towards a present misfortune. In this study we measured hedonic feelings, skin conductance, and brain activation patterns in 16 healthy volunteers who experienced moderate pain in two different contexts. In the "relative relief...

Variability in opioid analgesia has been attributed to many factors. For example, genetic variability of the μ-opioid receptor (MOR)-encoding gene introduces variability in MOR function and endogenous opioid neurotransmission. Emerging evidence suggests that personality trait related to the experience of reward is linked to endogenous opioid neurot...