The neurobiology of love and addiction: Central nervous system signaling and energy metabolism
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články, přehledy
PubMed
40760398
PubMed Central
PMC12464042
DOI
10.3758/s13415-025-01333-w
PII: 10.3758/s13415-025-01333-w
Knihovny.cz E-zdroje
- Klíčová slova
- Bioenergetics, Brain, Broken heart, Dopamine, Drug addiction, Nitric oxide, Relaxation response, Reward pathway, Romantic love, Stress,
- MeSH
- centrální nervový systém * metabolismus MeSH
- energetický metabolismus * fyziologie MeSH
- láska * MeSH
- lidé MeSH
- mozek * metabolismus MeSH
- návykové chování * metabolismus patofyziologie MeSH
- neurobiologie MeSH
- odměna MeSH
- oxid dusnatý metabolismus MeSH
- poruchy spojené s užíváním psychoaktivních látek * metabolismus patofyziologie MeSH
- signální transdukce * fyziologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- oxid dusnatý MeSH
Despite our ongoing fascination with love's pleasures and pain, psychologists and neurobiologists have only recently begun to explore the neurobiological connections shared by feelings of romantic love and the experience of drug addiction. Functional imaging studies have revealed that feelings resulting from romantic love and those resulting from active drug use both activate the central reward system, which is a series of forebrain and midbrain structures that transmit signals primarily via dopamine release. Similarly, the relaxation response, which is a series of behaviors designed to alleviate stress-related physiologic sequelae, may also be helpful as an adjunct therapy for drug withdrawal. The benefits of the relaxation response and related mind-body practices may stem directly from its impact on mitochondria, organelles that are central to balanced energy production. Nitric oxide (NO) is a central neurotransmitter and also a key regulatory molecule that modulates mitochondrial respiration and oxygen utilization. Thus, we propose that observed behaviorally mediated changes that emerge from engaging the relaxation response may be the result of NO-mediated improvements in mitochondrial bioenergetics. Future research might focus on elucidating the important links between cellular bioenergetics, the relaxation response, and the central reward system and might explore NO modulation as a potentially effective target for drug development.
Zobrazit více v PubMed
Acevedo, B. P., Aron, A., Fisher, H. E., & Brown, L. L. (2012). Neural correlates of long-term intense romantic love. PubMed DOI PMC
Acevedo, B. P., Poulin, M. J., Collins, N. L., & Brown, L. L. (2020). After the honeymoon: Neural and genetic correlates of romantic love in newlywed marriages. PubMed DOI PMC
Adams, M. L., Kalicki, J. M., Meyer, E. R., & Cicero, T. J. (1993). Inhibition of the morphine withdrawal syndrome by a nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester. PubMed DOI
American Psychological Association. (2018). Romantic love. In
American Psychological Association. (2018). Addiction. In
American Society of Addiction Medicine. (2019). Definition of addiction. https://www.asam.org/quality-care/definition-of-addiction
Aron, A., Fisher, H., Mashek, D. J., Strong, G., Li, H., & Brown, L. L. (2005). Reward, motivation, and emotion systems associated with early-stage intense romantic love. PubMed DOI
Attwell, D., & Laughlin, S. B. (2001). An energy budget for signaling in the grey matter of the brain. PubMed DOI
Beary, J. F., Benson, H., & Klemchuk, H. P. (1974). A simple psychophysiologic technique which elicits the hypometabolic changes of the relaxation response. PubMed DOI
Benson, H., Greenwood, M. M., & Klemchuk, H. (1975). The relaxation response: Psychophysiologic aspects and clinical applications. PubMed DOI
Bhasin, M. K., Denninger, J. W., Huffman, J. C., Joseph, M. G., Niles, H., Chad-Friedman, E., Goldman, R., Buczynski-Kelley, B., Mahoney, B. A., Fricchione, G. L., Dusek, J. A., Benson, H., Zusman, R. M., & Libermann, T. A. (2018). Specific transcriptome changes associated with blood pressure reduction in hypertensive patients after relaxation response training. PubMed DOI PMC
Bhasin, M. K., Dusek, J. A., Chang, B.-H., Joseph, M. G., Denninger, J. W., Fricchione, G. L., Benson, H., & Libermann, T. A. (2013). Relaxation response induces temporal transcriptome changes in energy metabolism, insulin secretion and inflammatory pathways. PubMed DOI PMC
Bressan, P., & Kramer, P. (2021). Mental health, mitochondria, and the battle of the sexes. PubMed DOI PMC
Black, D. S., & Slavich, G. M. (2016). Mindfulness meditation and the immune system: A systematic review of randomized controlled trials. PubMed DOI PMC
Brown, G. C., & Cooper, C. (1994). Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. PubMed DOI
Brown, R. P., & Gerbarg, P. L. (2005). Sudarshan kriya yogic breathing in the treatment of stress, anxiety, and depression: Part II—clinical applications and guidelines. PubMed DOI
Burkett, J. P., Spiegel, L. L., Inoue, K., Murphy, A. Z., & Young, L. J. (2011). Activation of μ-opioid receptors in the dorsal striatum is necessary for adult social attachment in monogamous prairie voles. PubMed DOI PMC
Buzsáki, G., & Draguhn, A. (2004). Neuronal oscillations in cortical networks. PubMed DOI
Calabrese, V., Mancuso, C., Calvani, M., Rizzarelli, E., Butterfield, D. A., & Stella, A. M. G. (2007). Nitric oxide in the central nervous system: Neuroprotection versus neurotoxicity. PubMed DOI
Carlsson, A. (2000).
Carter, C. S. (2017). The oxytocin–vasopressin pathway in the context of love and fear. PubMed PMC
Crews, F. T., Zou, J., & Qin, L. (2011). Induction of innate immune genes in brain create the neurobiology of addiction. PubMed DOI PMC
Cunha-Oliveira, T., Rego, A. C., & Oliveira, C. R. (2008). Cellular and molecular mechanisms involved in the neurotoxicity of opioid and psychostimulant drugs. PubMed DOI
Dhaliwal, A., & Gupta, M. (2023). Physiology, opioid receptor. In PubMed
Dromparis, P., & Michelakis, E. D. (2012). Mitochondria in vascular health and disease. PubMed DOI
Dusek, J. A., Chang, B. H., Zaki, J., Lazar, S., Deykin, A., Stefano, G. B., Wohlhueter, A. L., Hibberd, P. L., & Benson, H. (2006). Association between oxygen consumption and nitric oxide production during the relaxation response. PubMed
Epstein, F. H., Moncada, S., & Higgs, A. (1993). The L-arginine-nitric oxide pathway. PubMed DOI
Esch, T., & Stefano, G. B. (2004). The neurobiology of pleasure, reward processes, addiction and their health implications. PubMed
Esch, T., & Stefano, G. B. (2005). The neurobiology of love. PubMed
Esch, T., & Stefano, G. B. (2005). Love promotes health. PubMed
Esch, T., & Stefano, G. B. (2010). Endogenous reward mechanisms and their importance in stress reduction, exercise and the brain. PubMed DOI PMC
Esch, T. (2014). The neurobiology of meditation and mindfulness. In S. Schmidt spsampsps H. Walach (Eds.),
Esch, T., Kream, R. M., & Stefano, G. B. (2020). Emerging regulatory roles of opioid peptides, endogenous morphine, and opioid receptor subtypes in immunomodulatory processes: Metabolic, behavioral, and evolutionary perspectives. PubMed DOI
Esch, T., Stefano, G. B., & Michaelsen, M. M. (2024). The foundations of mind-body medicine: Love, good relationships, and happiness modulate stress and promote health. PubMed DOI
Fisher, H., Aron, A., & Brown, L. L. (2005). Romantic love: An fMRI study of a neural mechanism for mate choice. PubMed DOI
Fisher, H. E., Xu, X., Aron, A., & Brown, L. L. (2016). Intense, passionate, romantic love: A natural addiction? How the fields that investigate romance and substance abuse can inform each other. PubMed DOI PMC
Foerster, K., & Kanske, P. (2022). Upregulating positive affect through compassion: Psychological and physiological evidence. PubMed DOI
Fries, P. (2005). A mechanism for cognitive dynamics: Neuronal communication through neuronal coherence. PubMed DOI
Fu, Z. X., Tan, X., Fang, H., Lau, P. M., Wang, X., Cheng, H., & Bi, G. Q. (2017). Dendritic mitoflash as a putative signal for stabilizing long-term synaptic plasticity. PubMed DOI PMC
Furlan, A., & Petrus, P. (2023). Brain–body communication in metabolic control. PubMed DOI
Garner, M., Reith, W., & Krick, C. (2019). 10-week Hatha yoga increases right hippocampal density compared to active and passive control groups: A controlled structural cMRI study. DOI
Gautam, S., Saxena, R., Dada, T., & Dada, R. (2021). Yoga—impact on mitochondrial health: Clinical consequences. PubMed DOI PMC
Gautam, S., Kumar, U., Kumar, M., Rana, D., & Dada, R. (2021). Yoga improves mitochondrial health and reduces severity of autoimmune inflammatory arthritis: A randomized controlled trial. PubMed DOI
Gothe, N. P., Khan, I., Hayes, J., et al. (2019). Yoga effects on brain health: A systematic review of the current literature. PubMed DOI PMC
Gowri, M. M., Rajendran, J., Srinivasan, A., Bhavanani, A. B., & Meena, R. (2022). Impact of an integrated yoga therapy protocol on insulin resistance and glycemic control in patients with type 2 diabetes mellitus. PubMed DOI PMC
Hemish, J., Nakaya, N., Mittal, V., & Enikolopov, G. (2003). Nitric oxide activates diverse signaling pathways to regulate gene expression. PubMed DOI
Hervera, A., Negrete, R., Leánez, S., et al. (2011). Peripheral effects of morphine and expression of μ-opioid receptors in the dorsal root ganglia during neuropathic pain: Nitric oxide signaling. PubMed DOI PMC
Insel, T. R. (2010). The challenge of translation in social neuroscience: A review of oxytocin, vasopressin, and affiliative behavior. PubMed DOI PMC
Itzhak, Y., Martin, J. L., & Ali, S. F. (2000). Comparison between the role of the neuronal and inducible nitric oxide synthase in methamphetamine-induced neurotoxicity and sensitization. PubMed DOI
Iversen, S. D., & Iversen, L. L. (2007). Dopamine: 50 years in perspective. PubMed DOI
Kalamarides, D. J., Singh, A., & Dani, J. A. (2024). Protracted opioid withdrawal behaviors are reduced by nitric oxide inhibition in mice. DOI
Kann, O., Papageorgiou, I. E., & Draguhn, A. (2014). Highly energized inhibitory interneurons are a central element for information processing in cortical networks. PubMed DOI PMC
Karrasch, S., Mavioğlu, R. N., Matits, L., et al. (2023). Randomized controlled trial investigating potential effects of relaxation on mitochondrial function in immune cells: A pilot experiment. PubMed DOI
Kemper, K. J., Powell, D., Helms, C. C., & Kim-Shapiro, D. B. (2014). Loving-kindness meditation’s effects on nitric oxide and perceived well-being: A pilot study in experienced and inexperienced meditators. PubMed DOI
Kimes, A. S., Vaupel, D. B., & London, E. D. (1993). Attenuation of some signs of opioid withdrawal by inhibitors of nitric oxide synthase. PubMed DOI
Klajner, F., Hartman, L. M., & Sobell, M. B. (1984). Treatment of substance abuse by relaxation training: A review of its rationale, efficacy and mechanisms. PubMed DOI
Koob, G. F., & Volkow, N. D. (2016). Neurobiology of addiction: A neurocircuitry analysis. PubMed DOI PMC
Kream, R. M., & Stefano, G. B. (2009). Endogenous morphine and nitric oxide coupled regulation of mitochondrial processes. PubMed
Kross, E., Berman, M. G., Mischel, W., et al. (2011). Social rejection shares somatosensory representations with physical pain. PubMed DOI PMC
Lee, M. R., Scheidweiler, K. B., Diao, X. X., Akhlaghi, F., Cummins, A., Huestis, M. A., Leggio, L., & Averbeck, B. B. (2018). Oxytocin by intranasal and intravenous routes reaches the cerebrospinal fluid in rhesus macaques: Determination using a novel oxytocin assay. PubMed DOI PMC
Le Merrer, J., Becker, J. A. J., Befort, K., & Kieffer, B. L. (2009). Reward processing by the opioid system in the brain. PubMed DOI PMC
Lewis, R. G., Florio, E., Punzo, D., spsampsps Borrelli, E. (2021). The brain’s reward system in health and disease. In PubMed PMC
Leza, J. C., Lizasoain, I., Cuellar, B., et al. (1996). Correlation between brain nitric oxide synthase activity and opiate withdrawal. PubMed DOI
Lotfinia, S., Yaseri, A., Jamshidmofid, P., et al. (2024). Effect of relaxation-based virtual reality on psychological and physiological stress of substance abusers under detoxification: A randomized controlled trial. PubMed DOI PMC
Maechler, P., & Wollheim, C. B. (2001). Mitochondrial function in normal and diabetic β-cells. PubMed DOI
Majeed, N. H., Przewłocka, B., Machelska, H., & Przewłocki, R. (1994). Inhibition of nitric oxide synthase attenuates the development of morphine tolerance and dependence in mice. PubMed DOI
Mantione, K. J., Esch, T., & Stefano, G. B. (2007). Detection of nitric oxide in exhaled human breath: Exercise and resting determinations. PubMed
Marazziti, D., Palermo, S., spsampsps Mucci, F. (2021). The science of love: State of the art. In PubMed
Mastronicola, D., Arcuri, E., Arese, M., et al. (2004). Morphine but not fentanyl and methadone affects mitochondrial membrane potential by inducing nitric oxide release in glioma cells. PubMed DOI PMC
Murnane, K. S., Edinoff, A. N., Cornett, E. M., & Kaye, A. D. (2023). Updated perspectives on the neurobiology of substance use disorders using neuroimaging. PubMed DOI PMC
Murray, D. R., Haselton, M. G., Fales, M., & Cole, S. W. (2018). Falling in love is associated with immune system gene regulation. PubMed DOI PMC
Nathan, C. (1992). Nitric oxide as a secretory product of mammalian cells. PubMed DOI
National Institute on Drug Abuse. (2007).
Nestler, E. J. (2001). Molecular basis of long-term plasticity underlying addiction. PubMed DOI
Nestler, E. J. (2012). Transcriptional mechanisms of drug addiction. PubMed DOI PMC
Olds, J., & Schwartz, R. S. (2023). Why don’t you take this to a friend? A question psychotherapists should ask more often. PubMed DOI PMC
Peele, S., & Brodsky, A. (1975).
Peris, J., MacFadyen, K., Smith, J. A., et al. (2016). Oxytocin receptors are expressed on dopamine and glutamate neurons in the mouse ventral tegmental area that project to nucleus accumbens and other mesolimbic targets. PubMed DOI PMC
Picard, M., McEwen, B. S., Epel, E. S., & Sandi, C. (2018). An energetic view of stress: Focus on mitochondria. PubMed DOI PMC
Priest, C., & Tontonoz, P. (2019). Inter-organ cross-talk in metabolic syndrome. PubMed DOI
Radfar, A., Abohashem, S., Osborne, M. T., et al. (2021). Stress-associated neurobiological activity associates with the risk for and timing of subsequent Takotsubo syndrome. PubMed DOI PMC
Raut, A., Iglewski, M., & Ratka, A. (2006). Differential effects of impaired mitochondrial energy production on the function of mu and delta opioid receptors in neuronal SK-N-SH cells. PubMed DOI
Raut, A., Rao, V. R., & Ratka, A. (2007). Changes in opioid receptor proteins during mitochondrial impairment in differentiated SK-N-SH cells. PubMed DOI PMC
Rigney, N., De Vries, G. J., Petrulis, A., & Young, L. J. (2022). Oxytocin, vasopressin, and social behavior: From neural circuits to clinical opportunities. PubMed DOI PMC
Rinne, P., Lahnakoski, J. M., Saarimäki, H., et al. (2024). Six types of loves differentially recruit reward and social cognition brain areas. PubMed DOI PMC
Robison, A. J., & Nestler, E. J. (2011). Transcriptional and epigenetic mechanisms of addiction. PubMed DOI PMC
Roth-Deri, I., Green-Sadan, T., & Yadid, G. (2008). β-Endorphin and drug-induced reward and reinforcement. PubMed DOI
Rysztak, L. G., & Jutkiewicz, E. M. (2022). The role of enkephalinergic systems in substance use disorders. PubMed DOI PMC
Salamon, E., Esch, T., & Stefano, G. B. (2005). Role of amygdala in mediating sexual and emotional behavior via coupled nitric oxide release. PubMed DOI
Septimar, Z. M., Priatna, H., & Tomi, S. Y. (2021). Effect of Benson’s relaxation techniques on blood glucose levels in patients with diabetes mellitus. DOI
Seshadri, K. (2016). The neuroendocrinology of love. PubMed DOI PMC
Shyu, C., Chavez, S., Boileau, I., & Foll, B. L. (2022). Quantifying GABA in addiction: A review of proton magnetic resonance spectroscopy studies. PubMed DOI PMC
Song, H., Zou, Z., Kou, J., et al. (2015). Love-related changes in the brain: A resting-state functional magnetic resonance imaging study. PubMed DOI PMC
Stefano, G. B. (1999). The Mu3 opiate receptor subtype. DOI
Stefano, G. B., Fricchione, G. L., & Esch, T. (2006). Relaxation: Molecular and physiological significance. PubMed
Stefano, G. B., Esch, T., & Kream, R. M. (2019). Augmentation of whole-body metabolic status by mind-body training: Synchronous integration of tissue- and organ-specific mitochondrial function. PubMed DOI PMC
Stefano, G. B., & Esch, T. (2005). Love and stress. PubMed
Stefano, G. B., Goumon, Y., Bilfinger, T. V., Welters, I. D., & Cadet, P. (2000). Basal nitric oxide limits immune, nervous and cardiovascular excitation: Human endothelia express a mu opiate receptor. PubMed DOI
Stefano, G. B., & Kream, R. M. (2009). Dopamine, morphine, and nitric oxide: An evolutionary signaling triad. PubMed DOI PMC
Stefano, G. B., & Kream, R. M. (2011). Reciprocal regulation of cellular nitric oxide formation by nitric oxide synthase and nitrite reductases. PubMed DOI PMC
Stefano, G. B., & Kream, R. M. (2016). Dysregulated mitochondrial and chloroplast bioenergetics from a translational medical perspective. PubMed DOI PMC
Stefano, G. B., & Kream, R. M. (2017). Aging reversal and healthy longevity is in reach: Dependence on mitochondrial DNA heteroplasmy as a key molecular target. PubMed DOI PMC
Stefano, G. B., Mantione, K. J., Capellan, L., Casares, F. M., Challenger, S., Ramin, R., Samuel, J. M., Snyder, C., & Kream, R. M. (2015). Morphine stimulates nitric oxide release in human mitochondria. PubMed DOI
Stefano, G. B., Murga, J., Benson, H., Zhu, W., Bilfinger, T. V., & Magazine, H. I. (2001). Nitric oxide inhibits norepinephrine stimulated contraction of human internal thoracic artery and rat aorta. PubMed DOI
Stefano, G. B., Ptáček, R., Kuželová, H., & Kream, R. M. (2012). Endogenous morphine: Up-to-date review 2011. PubMed DOI
Tang, Y., Hölzel, B. K., & Posner, M. I. (2015). The neuroscience of mindfulness meditation. PubMed DOI
Toda, N., Kishioka, S., Hatano, Y., et al. (2008). Modulation of opioid actions by nitric oxide signaling. PubMed DOI
Toda, N., Kishioka, S., Hatano, Y., & Toda, H. (2009). Interactions between morphine and nitric oxide in various organs. PubMed DOI
Tomkins, D. M., & Sellers, E. M. (2001). Addiction and the brain: The role of neurotransmitters in the cause and treatment of drug dependence. PubMed PMC
Tracey, K. J. (2002). The inflammatory reflex. PubMed DOI
Valentino, R. J., & Volkow, N. D. (2018). Untangling the complexity of opioid receptor function. PubMed DOI PMC
Volkow, N. D., Fowler, J. S., & Wang, G.-J. (2003). The addicted human brain: Insights from imaging studies. PubMed DOI PMC
Volkow, N. D., Fowler, J. S., Wang, G.-J., et al. (2007). Dopamine in drug abuse and addiction. PubMed DOI
Volkow, N. D., Michaelides, M., & Baler, R. (2019). The neuroscience of drug reward and addiction. PubMed DOI PMC
Winick-Ng, W., Leri, F., & Kalisch, B. E. (2012). Nitric oxide and histone deacetylases modulate cocaine-induced mu-opioid receptor levels in PC12 cells. PubMed DOI PMC
Wittstein, I. S., Thiemann, D. R., Lima, J. A., et al. (2005). Neurohumoral features of myocardial stunning due to sudden emotional stress. PubMed DOI
Wronikowska-Denysiuk, O., Mrozek, W., & Budzyńska, B. (2023). The role of oxytocin and vasopressin in drug-induced reward—Implications for social and non-social factors. PubMed DOI PMC
Xu, R., Serritella, A. V., Sen, T., et al. (2013). Behavioral effects of cocaine mediated by nitric oxide-GAPDH transcriptional signaling. PubMed DOI PMC
Ye, J., & Medzhitov, R. (2019). Control strategies in systemic metabolism. PubMed DOI
Yellen, G. (2018). Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism. PubMed DOI PMC
Zalewska-Kaszubska, J., & Czarnecka, E. (2005). Deficit in beta-endorphin peptide and tendency to alcohol abuse. PubMed DOI
Zeki, S. (2007). The neurobiology of love. PubMed DOI
Zhu, W., Cadet, P., Baggerman, G., Mantione, K. J., & Stefano, G. B. (2005). Human white blood cells synthesize morphine: CYP2D6 modulation. PubMed DOI