Morphine sensitization is associated with increased locomotion and stereotypies in rats. This persistent condition has been proposed as a model of manic-like symptoms. Modifications in reward threshold are considered a central feature of mania and have been related to changes in mesocorticolimbic dopaminergic transmission. Thus, to further characterize this model, we investigated reward responses in morphine-sensitized male rats and the mechanisms underlying the behavioral phenotype. In particular, we examined the possible involvement of hyperpolarization-activated cyclic nucleotide-gated channels as they play a critical role in regulating the excitability of dopaminergic neurons. Rats were trained to self-administer sucrose to study whether morphine sensitization affected motivated behavior. Next, the dopaminergic response to sucrose was examined in the nucleus accumbens shell by in vivo microdialysis. To investigate the possible mechanisms underlying the increased dopaminergic transmission in morphine-sensitized rats, HCN2 channel expression levels in mesocorticolimbic regions were analyzed by immunoblotting. Sensitized rats showed an enhanced motivation to work for sucrose that was accompanied by an increased dopaminergic response to sucrose consumption in the nucleus accumbens shell. Moreover, HCN2 expression levels were increased in the ventral tegmental area, suggesting that their increased expression may underpin the enhanced motivation for sucrose reward and nucleus accumbens shell dopaminergic response in sensitized rats. The modified behavioral and dopaminergic reward response observed in sensitized rats supports the suggestion that the condition of morphine sensitization can be regarded as a model of manic symptoms.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/FBP.0000000000000545 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mu opioid receptors expressed in striatal D2 medium spiny neurons have divergent contributions to cocaine and morphine reward.
Neuroscience
January 2025
Institute for Neuroscience, The University of Texas at Austin, Austin, TX, USA; Waggoner Center for Alcohol & Addiction Research, The University of Texas at Austin, Austin, TX, USA; Department of Neuroscience, The University of Texas at Austin, Austin, TX, USA; Department of Neurology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA. Electronic address:
While our understanding of the neurobiological mechanisms underlying cocaine and opiate reward has historically been dopamine-focused, evidence from genetic and pharmacological approaches indicates that µ-opioid receptors (MORs) in the striatum are important contributors. Within the striatum, MORs are expressed in both dopamine D1-receptor and D2-receptor expressing GABAergic medium spiny neurons (MSNs), as well as in interneurons and various afferents. Thus, it remains unclear how these distinct MOR populations regulate drug reward.
View Article and Find Full Text PDFNeuroinflammatory history results in overlapping transcriptional signatures with heroin exposure in the nucleus accumbens and alters responsiveness to heroin in male rats.
Transl Psychiatry
December 2024
Center for Substance Abuse Research, Temple University, Philadelphia, PA, USA.
Recent progress in psychiatric research has highlighted neuroinflammation in the pathophysiology of opioid use disorder (OUD), suggesting that heightened immune responses in the brain may exacerbate opioid-related mechanisms. However, the molecular mechanisms resulting from neuroinflammation that impact opioid-induced behaviors and transcriptional pathways remain poorly understood. In this study, we have begun to address this critical knowledge gap by exploring the intersection between neuroinflammation and exposure to the opioid heroin, utilizing lipopolysaccharide (LPS)-induced neuroinflammation, to investigate transcriptional changes in the nucleus accumbens (NAc), an essential region in the mesolimbic dopamine system that mediates opioid reward.
View Article and Find Full Text PDFMu-opioid receptor knockout on Foxp2-expressing neurons reduces aversion-resistant alcohol drinking.
Pharmacol Biochem Behav
December 2024
Department of Psychology and Center for Neuroscience and Behavior, Miami University, Oxford, OH, USA. Electronic address:
Mu-opioid receptors (MORs) in the amygdala and striatum are important in addictive and rewarding behaviors. The transcription factor Foxp2 is a genetic marker of intercalated (ITC) cells in the amygdala and a subset of striatal medium spiny neurons (MSNs), both of which express MORs in wild-type mice and are neuronal subpopulations of potential relevance to alcohol-drinking behaviors. For the current series of studies, we characterized the behavior of mice with genetic deletion of the MOR gene Oprm1 in Foxp2-expressing neurons (Foxp2-Cre/Oprm1).
View Article and Find Full Text PDFThe function of the ZFP189 transcription factor in the nucleus accumbens facilitates cocaine-specific transcriptional and behavioral adaptations.
Mol Psychiatry
November 2024
Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
Distinguishing the brain mechanisms affected by distinct addictive drugs may inform targeted therapies against specific substance use disorders (SUDs). Here, we explore the function of a drug-associated, transcriptionally repressive transcription factor (TF), ZFP189, whose expression in the nucleus accumbens (NAc) facilitates cocaine-induced molecular and behavioral adaptations. To uncover the necessity of ZFP189-mediated transcriptional control in driving cocaine-induced behaviors, we created synthetic ZFP189 TFs of distinct transcriptional function, including ZFP189, which activates the expression of target genes and exerts opposite transcriptional control to the endogenously repressive ZFP189.
View Article and Find Full Text PDFPerioperative Duloxetine in Total Joint Arthroplasty: An Umbrella Review.
J Perianesth Nurs
November 2024
Department of Orthopedics, West China Hospital, West China School of Nursing, Sichuan University, Chengdu, Sichuan, China. Electronic address:
Purpose: Duloxetine, a serotonin and norepinephrine reuptake inhibitor primarily used for chronic neuropathic pain, has been debated for its efficacy in total joint arthroplasty contexts.
Design: Umbrella review.
Methods: A comprehensive search spanning PubMed, CINAHL, OVID, Embase, MEDLINE, CENTRAL, Google Scholar, and Cochrane, with no language restrictions up to January 2024, was conducted.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!