Evidence suggests that adults with a history of childhood maltreatment, the experience of emotional or physical neglect and/or abuse within the family during childhood, have blunted reward and stress processing, and higher risk of depression. The mu opioid receptor rich nucleus accumbens and amygdala are critical to reward and stress processing respectively. We hypothesized that nucleus accumbens and amygdala mu opioid receptor densities and activity (change in receptor binding due to endogenous opioid release or receptor conformation change) were negatively associated with childhood maltreatment in healthy young adults. Maltreatment was assessed with the Childhood Trauma Questionnaire (CTQ). Healthy participants, n = 75 (52% female) completed [C]carfentanil positron emission tomography imaging labeling mu opioid receptors. The relationship between CTQ score and binding potential (BP, proportional to density of unoccupied receptors) was evaluated with a linear mixed effects model. No significant relationship was found between CTQ score and BP ( = 3.28; = 1, 73; = 0.074) or change in BP (activity) ( = 1.48; = 198.3; = 0.14). This is the first investigation of mu opioid receptors in those with childhood maltreatment. We did not identify a significant relationship between mu opioid receptor dynamics and severity of maltreatment in those without psychopathology. Because this cohort has a low CTQ score average, this may indicate that those with low severity of maltreatment may not have associated changes in mu opioid receptor dynamics. Future directions include evaluating a cohort with increased severity of childhood maltreatment.
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http://dx.doi.org/10.1007/s40653-022-00463-4 | DOI Listing |
Br J Pharmacol
January 2025
Center for Clinical Pharmacology, Department of Anesthesiology, Washington University School of Medicine, St. Louis, Missouri, USA.
Background And Purpose: Pituitary adenylate cyclase activating polypeptide (PACAP) is a human migraine trigger that is being targeted for migraine. The δ-opioid receptor (δ-receptor) is a novel target for the treatment of migraine, but its mechanism remains unclear. The goals of this study were to develop a mouse PACAP-headache model using clinically significant doses of PACAP; determine the effects of δ-receptor activation in this model; and investigate the co-expression of δ-receptors, PACAP and PACAP-PAC1 receptor.
View Article and Find Full Text PDFNeuroscience
January 2025
Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran; Department of Physiology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran. Electronic address:
Corticosteroid signaling plays a critical role in modulating the neural systems underlying reward and addiction, but the specific contributions of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the medial prefrontal cortex (mPFC) to opioid reward and dopaminergic plasticity remain unclear. Here, we investigated the effects of intra-mPFC injection of corticosteroid receptor ligand (corticosterone; CORT), glucocorticoid receptor antagonist (RU38486; RU), and mineralocorticoid receptor antagonist (spironolactone; SP) on morphine-induced conditioned place preference (CPP) and dopamine transporter (DAT) expression in the mPFC. Adult male Wistar rats received intra-mPFC injections of CORT, RU, SP, or their respective vehicles prior to morphine CPP conditioning.
View Article and Find Full Text PDFRSC Med Chem
December 2024
Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara 44121 Ferrara Italy
The N/OFQ-NOP receptor is a fascinating peptidergic system with the potential to be exploited for the development of analgesic drugs devoid of side effects associated with classical opioid signalling modulation. To date, up to four X-ray and cryo-EM structures of the NOP receptor in complex with the endogenous peptide agonist N/OFQ and three small molecule antagonists have been solved and released. Despite the available structural information, the details of selective small molecule agonist binding to the NOP receptor in the active state remain elusive.
View Article and Find Full Text PDFBr J Anaesth
January 2025
Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Anesthesiology, Weill Cornell Medicine, New York, NY, USA. Electronic address:
The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.
View Article and Find Full Text PDFJ Toxicol Sci
January 2025
Department of Pharmaceutical and Environmental Sciences, Tokyo Metropolitan Institute of Public Health.
In illicit drug markets, the most recently expanding new synthetic opioid subclass is benzimidazoles, also known as nitazenes, which were originally developed as analgesics in the 1950s. The emergence of this classical, potent drug family has attracted extensive research interest in the field of forensic toxicology; however, information on their psychological and physical dependence is very limited. Herein, we evaluated the rewarding effects of four nitazene analogs using a battery of in vivo experiments, with a positive control drug (isotonitazene).
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