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Stephen D Mague

Assistant Professor in Psychiatry and Behavioral Sciences
Psychiatry & Behavioral Sciences, Behavioral Medicine & Neurosciences
3209, Bryan Research Building; Rm 361, Durham, NC 27710
3209, Bryan Research Building; Rm 421, Durham, NC 27710

Selected Publications


Electome network factors: Capturing emotional brain networks related to health and disease.

Journal Article Cell Rep Methods · January 22, 2024 Therapeutic development for mental disorders has been slow despite the high worldwide prevalence of illness. Unfortunately, cellular and circuit insights into disease etiology have largely failed to generalize across individuals that carry the same diagnos ... Full text Link to item Cite

Prenatal environmental stressors impair postnatal microglia function and adult behavior in males.

Journal Article Cell Rep · August 2, 2022 Gestational exposure to environmental toxins and socioeconomic stressors is epidemiologically linked to neurodevelopmental disorders with strong male bias, such as autism. We model these prenatal risk factors in mice by co-exposing pregnant dams to an envi ... Full text Link to item Cite

Brain-wide electrical dynamics encode individual appetitive social behavior.

Journal Article Neuron · May 18, 2022 The architecture whereby activity across many brain regions integrates to encode individual appetitive social behavior remains unknown. Here we measure electrical activity from eight brain regions as mice engage in a social preference assay. We then use ma ... Full text Link to item Cite

Brain-wide Electrical Spatiotemporal Dynamics Encode Depression Vulnerability.

Journal Article Cell · March 22, 2018 Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors w ... Full text Link to item Cite

Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

Journal Article Neuron · July 20, 2016 Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1 Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illne ... Full text Link to item Cite

Nucleus Accumbens AMPA Receptors Are Necessary for Morphine-Withdrawal-Induced Negative-Affective States in Rats.

Journal Article J Neurosci · May 25, 2016 UNLABELLED: Dependence is a hallmark feature of opiate addiction and is defined by the emergence of somatic and affective withdrawal signs. The nucleus accumbens (NAc) integrates dopaminergic and glutamatergic inputs to mediate rewarding and aversive prope ... Full text Link to item Cite

Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.

Journal Article Nat Commun · May 10, 2016 Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout m ... Full text Open Access Link to item Cite

Mouse model of OPRM1 (A118G) polymorphism has altered hippocampal function.

Journal Article Neuropharmacology · October 2015 A single nucleotide polymorphism (SNP) in the human μ-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in a variety of drug addiction and pain sensitivity phenotypes; however, the extent of these adaptations and the mechanisms ... Full text Link to item Cite

A common single nucleotide polymorphism A118G of the μ opioid receptor alters its N-glycosylation and protein stability.

Journal Article Biochem J · January 1, 2012 The A118G SNP (single nucleotide polymorphism) of the hMOPR [human MOPR (μ opioid receptor)] gene OPRM1 results in an amino acid substitution (N40D). Subjects homozygous for the 118G allele have been reported to require higher morphine doses to achieve ade ... Full text Link to item Cite

OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models.

Journal Article Drug Alcohol Depend · May 1, 2010 Endogenous opioids acting at mu-opioid receptors mediate many biological functions. Pharmacological intervention at these receptors has greatly aided in the treatment of acute and chronic pain, in addition to other uses. However, the development of toleran ... Full text Link to item Cite

Sex differences in response to nicotine in C57Bl/6:129SvEv mice.

Journal Article Nicotine Tob Res · July 2009 INTRODUCTION: Human studies suggest that smoking behavior in men may depend more on the pharmacological effects of nicotine, whereas in women, this behavior may rely more on nonpharmacological factors associated with smoking. Investigation of these paramet ... Full text Link to item Cite

Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior.

Journal Article Proc Natl Acad Sci U S A · June 30, 2009 A single nucleotide polymorphism (SNP) in the human mu-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in a variety of drug addiction and pain sensitivity phenotypes; however, the extent of these adaptations and the mechanism ... Full text Link to item Cite

Anatomically dissociable effects of dopamine D1 receptor agonists on reward and relief of withdrawal in morphine-dependent rats.

Journal Article Psychopharmacology (Berl) · June 2009 RATIONALE: Chronic opiate administration induces neuroadaptations within the nucleus accumbens (NAc) and ventral tegmental area (VTA) that can contribute to dependence. We have shown that morphine dependence shifts the behavioral consequences of D1 dopamin ... Full text Link to item Cite

Elevations of FosB in the nucleus accumbens during forced cocaine abstinence correlate with divergent changes in reward function.

Journal Article Neuroscience · July 13, 2007 Dysregulation of hedonic processing, in which seeking of drug reward becomes more desirable than seeking natural rewards, like food, sex, and novelty, is a consequence of chronic drug exposure and potentially leads to escalating drug usage and addiction. H ... Full text Link to item Cite

Behavioral and molecular effects of dopamine D1 receptor stimulation during naloxone-precipitated morphine withdrawal.

Journal Article J Neurosci · June 14, 2006 Morphine dependence is characterized by somatic and motivational signs of withdrawal that likely contribute to the maintenance of addictive behavior. The nucleus accumbens (NAc) receives extensive dopaminergic input and is an important substrate for mediat ... Full text Link to item Cite

Behavioral effects of short-term administration of lithium and valproic acid in rats.

Journal Article Brain Res · June 6, 2006 Lithium and valproic acid are mood-stabilizing agents that are often used to manage the episodes of mania and depression that characterize bipolar disorder. These agents develop clinical efficacy with chronic treatment, but the neurobiological actions that ... Full text Link to item Cite

Antidepressant-like effects of cranial stimulation within a low-energy magnetic field in rats.

Journal Article Biol Psychiatry · March 15, 2005 BACKGROUND: Evidence suggests that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) has mood-elevating actions in humans during the depressive phases of bipolar disorder. We examine ... Full text Link to item Cite

Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats.

Journal Article Biol Psychiatry · February 15, 2005 BACKGROUND: Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. We showed previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (F ... Full text Link to item Cite

Electome network factors: Capturing emotional brain networks related to health and disease.

Journal Article Cell Rep Methods · January 22, 2024 Therapeutic development for mental disorders has been slow despite the high worldwide prevalence of illness. Unfortunately, cellular and circuit insights into disease etiology have largely failed to generalize across individuals that carry the same diagnos ... Full text Link to item Cite

Prenatal environmental stressors impair postnatal microglia function and adult behavior in males.

Journal Article Cell Rep · August 2, 2022 Gestational exposure to environmental toxins and socioeconomic stressors is epidemiologically linked to neurodevelopmental disorders with strong male bias, such as autism. We model these prenatal risk factors in mice by co-exposing pregnant dams to an envi ... Full text Link to item Cite

Brain-wide electrical dynamics encode individual appetitive social behavior.

Journal Article Neuron · May 18, 2022 The architecture whereby activity across many brain regions integrates to encode individual appetitive social behavior remains unknown. Here we measure electrical activity from eight brain regions as mice engage in a social preference assay. We then use ma ... Full text Link to item Cite

Brain-wide Electrical Spatiotemporal Dynamics Encode Depression Vulnerability.

Journal Article Cell · March 22, 2018 Brain-wide fluctuations in local field potential oscillations reflect emergent network-level signals that mediate behavior. Cracking the code whereby these oscillations coordinate in time and space (spatiotemporal dynamics) to represent complex behaviors w ... Full text Link to item Cite

Dysregulation of Prefrontal Cortex-Mediated Slow-Evolving Limbic Dynamics Drives Stress-Induced Emotional Pathology.

Journal Article Neuron · July 20, 2016 Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1 Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illne ... Full text Link to item Cite

Nucleus Accumbens AMPA Receptors Are Necessary for Morphine-Withdrawal-Induced Negative-Affective States in Rats.

Journal Article J Neurosci · May 25, 2016 UNLABELLED: Dependence is a hallmark feature of opiate addiction and is defined by the emergence of somatic and affective withdrawal signs. The nucleus accumbens (NAc) integrates dopaminergic and glutamatergic inputs to mediate rewarding and aversive prope ... Full text Link to item Cite

Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.

Journal Article Nat Commun · May 10, 2016 Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout m ... Full text Open Access Link to item Cite

Mouse model of OPRM1 (A118G) polymorphism has altered hippocampal function.

Journal Article Neuropharmacology · October 2015 A single nucleotide polymorphism (SNP) in the human μ-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in a variety of drug addiction and pain sensitivity phenotypes; however, the extent of these adaptations and the mechanisms ... Full text Link to item Cite

A common single nucleotide polymorphism A118G of the μ opioid receptor alters its N-glycosylation and protein stability.

Journal Article Biochem J · January 1, 2012 The A118G SNP (single nucleotide polymorphism) of the hMOPR [human MOPR (μ opioid receptor)] gene OPRM1 results in an amino acid substitution (N40D). Subjects homozygous for the 118G allele have been reported to require higher morphine doses to achieve ade ... Full text Link to item Cite

OPRM1 SNP (A118G): involvement in disease development, treatment response, and animal models.

Journal Article Drug Alcohol Depend · May 1, 2010 Endogenous opioids acting at mu-opioid receptors mediate many biological functions. Pharmacological intervention at these receptors has greatly aided in the treatment of acute and chronic pain, in addition to other uses. However, the development of toleran ... Full text Link to item Cite

Sex differences in response to nicotine in C57Bl/6:129SvEv mice.

Journal Article Nicotine Tob Res · July 2009 INTRODUCTION: Human studies suggest that smoking behavior in men may depend more on the pharmacological effects of nicotine, whereas in women, this behavior may rely more on nonpharmacological factors associated with smoking. Investigation of these paramet ... Full text Link to item Cite

Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior.

Journal Article Proc Natl Acad Sci U S A · June 30, 2009 A single nucleotide polymorphism (SNP) in the human mu-opioid receptor gene (OPRM1 A118G) has been widely studied for its association in a variety of drug addiction and pain sensitivity phenotypes; however, the extent of these adaptations and the mechanism ... Full text Link to item Cite

Anatomically dissociable effects of dopamine D1 receptor agonists on reward and relief of withdrawal in morphine-dependent rats.

Journal Article Psychopharmacology (Berl) · June 2009 RATIONALE: Chronic opiate administration induces neuroadaptations within the nucleus accumbens (NAc) and ventral tegmental area (VTA) that can contribute to dependence. We have shown that morphine dependence shifts the behavioral consequences of D1 dopamin ... Full text Link to item Cite

Elevations of FosB in the nucleus accumbens during forced cocaine abstinence correlate with divergent changes in reward function.

Journal Article Neuroscience · July 13, 2007 Dysregulation of hedonic processing, in which seeking of drug reward becomes more desirable than seeking natural rewards, like food, sex, and novelty, is a consequence of chronic drug exposure and potentially leads to escalating drug usage and addiction. H ... Full text Link to item Cite

Behavioral and molecular effects of dopamine D1 receptor stimulation during naloxone-precipitated morphine withdrawal.

Journal Article J Neurosci · June 14, 2006 Morphine dependence is characterized by somatic and motivational signs of withdrawal that likely contribute to the maintenance of addictive behavior. The nucleus accumbens (NAc) receives extensive dopaminergic input and is an important substrate for mediat ... Full text Link to item Cite

Behavioral effects of short-term administration of lithium and valproic acid in rats.

Journal Article Brain Res · June 6, 2006 Lithium and valproic acid are mood-stabilizing agents that are often used to manage the episodes of mania and depression that characterize bipolar disorder. These agents develop clinical efficacy with chronic treatment, but the neurobiological actions that ... Full text Link to item Cite

Antidepressant-like effects of cranial stimulation within a low-energy magnetic field in rats.

Journal Article Biol Psychiatry · March 15, 2005 BACKGROUND: Evidence suggests that a novel type of magnetic resonance imaging (MRI) scan called echo planar magnetic resonance spectroscopic imaging (EP-MRSI) has mood-elevating actions in humans during the depressive phases of bipolar disorder. We examine ... Full text Link to item Cite

Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats.

Journal Article Biol Psychiatry · February 15, 2005 BACKGROUND: Brain phospholipid metabolism and membrane fluidity may be involved in the pathophysiology of mood disorders. We showed previously that cytidine, which increases phospholipid synthesis, has antidepressant-like effects in the forced swim test (F ... Full text Link to item Cite

Early developmental exposure to methylphenidate reduces cocaine-induced potentiation of brain stimulation reward in rats.

Journal Article Biol Psychiatry · January 15, 2005 BACKGROUND: Methylphenidate (MPH) is prescribed for the treatment of attention and hyperactivity disorders. We showed previously that early developmental exposure to MPH in rats causes behavioral alterations during adulthood, including reduced cocaine rewa ... Full text Link to item Cite

NMDA receptor antagonists ameliorate the stepping deficits produced by unilateral medial forebrain bundle injections of 6-OHDA in rats.

Journal Article Psychopharmacology (Berl) · September 2004 RATIONALE AND OBJECTIVES: To test the hypothesis that excess glutamatergic transmission at NMDA receptors may contribute to the pathogenesis of Parkinson's disease (PD), we examined the effects of various NMDA receptor antagonists on a recently developed r ... Full text Link to item Cite

Enduring behavioral effects of early exposure to methylphenidate in rats.

Journal Article Biol Psychiatry · December 15, 2003 BACKGROUND: Methylphenidate (MPH) is a stimulant prescribed for the treatment of attention-deficit/hyperactivity disorder (ADHD). Stimulant drugs can cause enduring behavioral adaptations, including altered drug sensitivity, in laboratory animals. We exami ... Full text Link to item Cite

Antidepressant-like effects of kappa-opioid receptor antagonists in the forced swim test in rats.

Journal Article J Pharmacol Exp Ther · April 2003 We showed previously that cAMP response element-binding protein (CREB) within the nucleus accumbens (NAc) of rats regulates immobility in the forced swim test (FST), an assay used to study depression. Because CREB regulates expression of dynorphin (which a ... Full text Link to item Cite