Patrick E. Rothwell
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Striatal pathology in Spinocerebellar Ataxia Type 1 mice: A comparative study with Huntington’s disease Open
Spinocerebellar ataxia type 1 (SCA1) and Huntington’s disease (HD), are motor diseases caused by CAG expansions in ATXN1 and HTT , where SCA1 shows prominent cerebellar neurodegeneration and HD shows prominent striatal neurodegeneration, p…
View article: VGF in the Nucleus Accumbens Regulates Synaptic and Opioid-Evoked Plasticity
VGF in the Nucleus Accumbens Regulates Synaptic and Opioid-Evoked Plasticity Open
Neuropeptides contribute to the functional complexity of the nucleus accumbens, and evaluating the mechanisms by which they influence reward neurocircuitry may reveal novel therapeutic targets. In this study, we investigated the role of th…
View article: Inhibition of the angiotensin-converting enzyme N-terminal catalytic domain prevents endogenous opioid degradation in brain tissue
Inhibition of the angiotensin-converting enzyme N-terminal catalytic domain prevents endogenous opioid degradation in brain tissue Open
Natural opioid signals in the brain produced by Met-enkephalin-Arg-Phe are enhanced after blocking its degradation by the N-terminal catalytic domain of angiotensin-converting enzyme.
View article: Exploiting the angiotensin-converting enzyme pathway to augment endogenous opioid signaling
Exploiting the angiotensin-converting enzyme pathway to augment endogenous opioid signaling Open
Angiotensin Converting Enzyme (ACE) impacts hemodynamics by regulating the conversion of angiotensin I to the vasoconstricting angiotensin II. We recently identified a non-canonical central role of ACE in the degradation of enkephalin hept…
View article: Synaptic Dysfunction and Compensation After NMDA Receptor Ablation in the Mouse Medial Prefrontal Cortex
Synaptic Dysfunction and Compensation After NMDA Receptor Ablation in the Mouse Medial Prefrontal Cortex Open
N-methyl-D-aspartate receptors (NMDARs) in the prefrontal cortex (PFC) are critical regulators of neuronal excitability, synaptic plasticity, and cognitive function. NMDAR disruptions, including pharmacological blockade and anti-NMDAR ence…
16p11.2 duplication shows early male-biased impacts on reward learning, but NMDA receptor antagonism reduces optimal choice selection in both wildtypes and 16p11.2 duplication Open
Rationale 16p11.2 duplication is associated with numerous neuropsychiatric conditions at a genome-wide level, including psychosis. Mice modeling 16p11.2 duplication may provide important insights into cognitive risk factors, in particular …
View article: Exploiting the Angiotensin-Converting Enzyme Pathway to Augment Endogenous Opioid Signaling
Exploiting the Angiotensin-Converting Enzyme Pathway to Augment Endogenous Opioid Signaling Open
Angiotensin Converting Enzyme (ACE) impacts hemodynamics by regulating the conversion of angiotensin I to the vasoconstricting angiotensin II. We recently identified a non-canonical central role of ACE in the degradation of enkephalin hept…
View article: Inhibition of the angiotensin-converting enzyme N-terminal catalytic domain prevents endogenous opioid degradation in brain tissue
Inhibition of the angiotensin-converting enzyme N-terminal catalytic domain prevents endogenous opioid degradation in brain tissue Open
Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin peptides in the periphery, and can also regulate endogenous opioid signaling by degrading enkephalin peptides in the brain. ACE has two catalytic domains,…
Mu opioid receptor expression by nucleus accumbens inhibitory interneurons promotes affiliative social behavior Open
Mu opioid receptors in the nucleus accumbens regulate motivated behavior, including pursuit of natural rewards like social interaction as well as exogenous opioids. We used a suite of genetic and viral strategies to conditionally delete mu…
Individual differences in decision-making shape how mesolimbic dopamine regulates choice confidence and change-of-mind Open
Nucleus accumbens dopamine signaling is an important neural substrate for decision-making. Dominant theories generally discretize and homogenize decision-making, when it is in fact a continuous process, with evaluation and re-evaluation co…
Sex Differences in Morphine Sensitivity of Neuroligin-3 Knockout Mice Open
Sex has a strong influence on the prevalence and course of brain conditions, including autism spectrum disorders. The mechanistic basis for these sex differences remains poorly understood, due in part to historical bias in biomedical resea…
View article: Modulation of endogenous opioid signaling by inhibitors of puromycin sensitive aminopeptidase
Modulation of endogenous opioid signaling by inhibitors of puromycin sensitive aminopeptidase Open
The endogenous opioid system regulates pain through local release of neuropeptides and modulation of their action on opioid receptors. However, the effect of opioid peptides, the enkephalins, is short-lived due to their rapid hydrolysis by…
Neuroligin‐3 in dopaminergic circuits promotes behavioural and neurobiological adaptations to chronic morphine exposure Open
Chronic opioid exposure causes structural and functional changes in brain circuits, which may contribute to opioid use disorders. Synaptic cell‐adhesion molecules are prime candidates for mediating this opioid‐evoked plasticity. Neuroligin…
Differential Patterns of Synaptic Plasticity in the Nucleus Accumbens Caused by Continuous and Interrupted Morphine Exposure Open
Opioid exposure and withdrawal both cause adaptations in brain circuits that may contribute to abuse liability. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systema…
Differential Patterns of Synaptic Plasticity in the Nucleus Accumbens Caused by Continuous and Interrupted Morphine Exposure Open
Opioid exposure and withdrawal both cause adaptations in brain circuits that may contribute to abuse liability. These adaptations vary in magnitude and direction following different patterns of opioid exposure, but few studies have systema…
Characterization and mu opioid receptor sensitivity of neuropeptide Y interneurons in the nucleus accumbens Open
Inhibitory interneurons represent less than 5% of neurons within the nucleus accumbens, but are critical for proper microcircuit function within this brain region. In the dorsal striatum, neuropeptide Y is expressed by two interneuron subt…
Neuroligin-3 in Dopaminergic Circuits Promotes Behavioral and Neurobiological Adaptations to Chronic Morphine Exposure Open
Chronic opioid exposure causes structural and functional changes in brain circuits, which may contribute to opioid use disorders. Synaptic cell-adhesion molecules are prime candidates for mediating this opioid-evoked plasticity. Neuroligin…
View article: Angiotensin-converting enzyme gates brain circuit–specific plasticity via an endogenous opioid
Angiotensin-converting enzyme gates brain circuit–specific plasticity via an endogenous opioid Open
Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is especially abundant in striatal tissue, but the function of ACE in striatal circuits remains poorly unde…
View article: Angiotensin-converting enzyme governs endogenous opioid signaling and synaptic plasticity in nucleus accumbens
Angiotensin-converting enzyme governs endogenous opioid signaling and synaptic plasticity in nucleus accumbens Open
Angiotensin-converting enzyme (ACE) regulates blood pressure by cleaving angiotensin I to produce angiotensin II. In the brain, ACE is expressed at uniquely high levels in the striatonigral pathway, but its central function remains poorly …
μ-Opioid Receptor (Oprm1) Copy Number Influences Nucleus Accumbens Microcircuitry and Reciprocal Social Behaviors Open
The μ-opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction, through actions in the nucleus accumbens. Here, we studied nucleus accumbens microcircuitry and social behavior in mal…
Effect of Aggressive Experience in Female Syrian Hamsters on Glutamate Receptor Expression in the Nucleus Accumbens Open
Our social relationships determine our health and well-being. In rodent models, there is now strong support for the rewarding properties of aggressive or assertive behaviors to be critical for the expression and development of adaptive soc…
Mu Opioid Receptor Gene Dosage Influences Reciprocal Social Behaviors and Nucleus Accumbens Microcircuitry Open
The mu opioid receptor regulates reward derived from both drug use and natural experiences, including social interaction. Homozygous genetic knockout of the mu opioid receptor (Oprm1−/−) causes social deficits in mice, whereas partial dysr…