About

Patrick R. Sweeney is an Assistant Professor of Molecular & Integrative Physiology at the University of Illinois. His research focuses on neural circuitry regulating feeding and emotion, with particular emphasis on the central melanocortin system. This system, composed of pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons in the hypothalamic arcuate nucleus, senses changes in energy stores via leptin and communicates this information to various brain regions. Mutations in this pathway are linked to obesity, with MC4R mutations being the most common cause of severe monogenetic obesity in humans. Sweeney's lab employs multidisciplinary approaches including in vivo calcium imaging, optogenetics, chemogenetics, neuropharmacology, light sheet imaging, and single-cell RNA sequencing to understand how these neural circuits influence feeding behavior, motivation, and emotional regulation. His work aims to develop new approaches for treating human diseases related to energy homeostasis and emotion, such as anorexia nervosa.

Research topics

• Biology
• Internal medicine
• Neuroscience
• Medicine
• Endocrinology
• Psychiatry
• Genetics
• Psychology

Selected publications

• Elevated activity of the mesolimbic dopamine system promotes feeding during pregnancy in mice

  Molecular Metabolism · 2026-01-24 · 1 citations

  articleOpen accessSenior authorCorresponding

  The pregnancy period is accompanied by increased feeding behavior to accommodate the elevated energy demands associated with fetal growth and development. However, the underlying neural circuitry and molecular mechanisms mediating increased feeding during pregnancy are largely unknown. Here, we utilized a combination of fiber photometry, chemogenetics, and mouse behavioral assays to characterize altered feeding behavior during pregnancy in mice. We uncover that pregnancy increases the average activity of the mesolimbic dopamine system during feeding behavior in mice. VTA dopamine neurons promote increased high fat diet feeding during pregnancy as inhibition of these cells selectively reduces acute high fat diet intake in pregnant mice. Further, pregnant mice exhibit increased sensitivity to food deprivation, an effect which requires activity of the mesolimbic dopamine system. Together, these findings provide a circuit basis mediating altered palatable food intake and sensitivity to negative energy balance during pregnancy in mice. • Average VTA dopamine response to palatable food is increased during pregnancy • Average VTA dopamine neuron activity is increased in response to negative energy balance during pregnancy • Nucleus accumbens dopamine levels are increased during feeding in pregnant mice • VTA dopamine neuron activity regulates palatable food intake and fast-induced refeeding in pregnant mice

  PublisherDOI

• Modeling Tools for Maximizing Behavioral Effects of tDCS Through Optimized Methodological Parameters

  Brain stimulation · 2025-07-01

  articleOpen access

  The ability to maintain and/or enhance aspects of cognition that can aid in military performance is of interest to the U.S. Army.However, in doing so, it is possible to also achieve non-targeted effects that may have negative consequences for performance.A study was completed that included 27 healthy, well-rested, active-duty Soldiers.Active and sham tDCS was applied for 30 minutes at 2 mA targeting the left dorsolateral prefrontal cortex (three conditions: active-anodal, active-cathodal, and sham).A variety of cognitive tasks relevant to military task performance were completed.Additional cognitive tasks were performed to assess potential negative performance tradeoffs.Performance improvements were found for sustained attention (active-anodal) for males in reaction time (p0.024,h p 2 0.16) and for sensitivity index in females (p0.013,h p 2 0.18).In addition, faster reaction times (p0.034,h p 2 0.15) and increased accuracy (p0.029,h p 2 0.16) associated with executive function (active-anodal and -cathodal) were found, and worsened working memory performance (active-cathodal; p0.008, h p 2 0.18).Finally, it was found that participants had increased risk-taking with active-anodal (p0.001,h p 2 0.33).When considering military tasks, increases in risk-taking could have the potential for negative effects if it results in placing the individual in a dangerous situation.In addition to cognitive tasks, a marksmanship task was performed.For this task, throughput (hits/second) was evaluated.It was found that participants performed better in both active conditions compared to the sham condition, F(2, 32) 0.037, h p 2 0.19.Thus, the use of tDCS in healthy military populations may show some promise for maintaining or enhancing performance; however, potential negative effects associated with its use needs to be more thoroughly evaluated.Additionally, there are still no guidelines regarding the frequency of using tDCS or any associated long-term effects that may occur.

  PublisherOA PDFDOI

• AB147. SOH25_AB_377. An audit of the prescription and implementation of spinal precautions in patients with actual or suspected spinal cord injuries at a level 3 university teaching hospital

  Mesentery and Peritoneum · 2025-03-01

  articleOpen access1st authorCorresponding
  PublisherDOI

• Elevated activity of the mesolimbic dopamine system promotes feeding during pregnancy in mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-10-22

  preprintOpen accessSenior authorCorresponding

  Summary The pregnancy period is accompanied by increased feeding behavior to accommodate the elevated energy demands associated with fetal growth and development. However, the underlying neural circuitry and molecular mechanisms mediating increased feeding during pregnancy are largely unknown. Here, we utilize a combination of fiber photometry, chemogenetics, and mouse behavioral assays to characterize altered feeding behavior during pregnancy in mice. We uncover that pregnancy increases the activity of the mesolimbic dopamine system during both homeostatic and hedonic feeding behavior in mice. VTA dopamine neurons are ultimately required for promoting increased hedonic feeding during pregnancy as inhibition of these cells selectively reduces acute high fat diet intake in pregnant mice. Further, pregnant mice exhibit increased sensitivity to food deprivation, an effect which requires activity of the mesolimbic dopamine system. Together, these findings provide a circuit basis mediating altered hedonic feeding behavior and sensitivity to negative energy balance during pregnancy in mice. Highlights VTA dopamine neurons show enhanced responsivity to palatable food during pregnancy VTA dopamine neurons show enhanced responsivity to negative energy balance during pregnancy Nucleus accumbens dopamine is increased during homeostatic and hedonic feeding in pregnant mice VTA dopamine neuron activity regulates hedonic eating and fast-induced refeeding in pregnant mice

  PublisherOA PDFDOI

• Preoperative patient education in vascular surgery

  Health Education Research · 2025-08-12

  article

  This is a systematic review and meta-analysis of preoperative patient education interventions used in vascular surgery and their impact on patient knowledge. Embase, PubMed, and Ovid were searched in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. For inclusion, studies involved an educational intervention for a vascular surgery procedure and patient knowledge was an outcome. Using mean knowledge scores (defined as the percentage of correct responses on knowledge assessments) pre and post education intervention for experimental groups, a forest plot with standardized mean difference (SMD) was generated. Subgroup analyses were performed for abdominal aortic aneurysm (AAA) repair and decision aids. Six studies (654 patients) met inclusion criteria (five randomized controlled trials, one prospective cohort study). Procedures included AAA repair, femoral-popliteal artery bypass, carotid surgery, and endovenous thermal vein ablation. Education interventions included informed consent discussions, decision aids, virtual reality displays, and videos. The pooled SMD was 0.64 (95% confidence interval [CI], 0.48-0.79), suggesting a significant positive effect of education interventions on patient knowledge. For AAA repair and decision aid subgroups (four papers each), the SMD was 0.58 (95% CI, 0.42-0.75) and 0.62 (95% CI, 0.45-0.79), respectively. Preoperative patient education enhances understanding of vascular surgery procedures. Developing procedure-specific and patient-oriented education interventions will help address knowledge gaps among patients with vascular disease.

  PublisherDOI

• Reduced melanocortin tone mediates increased feeding during pregnancy in mice

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-08-28

  preprintOpen accessSenior authorCorresponding

  Summary During pregnancy mammals increase their food intake to accommodate the elevated metabolic demands associated with fetal growth and development. However, the molecular and neural circuit mechanisms mediating increased feeding during pregnancy are largely unknown. Here, we demonstrate that arcuate nucleus agouti-related peptide (AgRP) neurons are activated and pro-opiomelanocortin (POMC) neurons are inhibited during pregnancy in mice. These changes are required for promoting hyperphagia during pregnancy as chemogenetic inhibition of AgRP neurons or activation of POMC neurons both reduced the feeding of pregnant mice to non-pregnant levels. Finally, we utilized single cell resolution spatial transcriptomics in the arcuate nucleus of non-pregnant and pregnant mice to characterize pregnancy-induced changes in the transcriptomic state of arcuate nucleus neurons, including significant changes in both AgRP and POMC neurons. Together, these findings outline a circuit mechanism mediating increased feeding during pregnancy, providing important mechanistic insights related to conditions at the intersection of reproduction and metabolism. Highlights AgRP neuron activity is increased and POMC neuron activity is decreased in pregnant mice Increased AgRP neuron activity and reduced POMC neuron activity is required for increased feeding during pregnancy Pregnancy enhances responsivity of AgRP neurons to palatable food Pregnancy drastically alters the transcriptional state of both AgRP and POMC neurons towards positive energy balance

  PublisherOA PDFDOI

• Medial hypothalamic MC3R signalling regulates energy rheostasis in adult mice

  The Journal of Physiology · 2024-12-24 · 2 citations

  articleOpen accessSenior authorCorresponding

  Although mammals resist both acute weight loss and weight gain, the neural circuitry mediating bi-directional defense against weight change is incompletely understood. Global constitutive deletion of the melanocortin-3-receptor (MC3R) impairs the behavioural response to both anorexic and orexigenic stimuli, with MC3R knockout mice demonstrating increased weight gain following anabolic challenges and increased weight loss following anorexic challenges (i.e. impaired energy rheostasis). However, the brain regions mediating this phenotype are not well understood. Here, we utilized MC3R floxed mice and viral injections of Cre-recombinase to selectively delete MC3R from the medial hypothalamus (MH) in adult mice. Behavioural assays were performed on these animals to test the role of MC3R in MH in the acute response to orexigenic and anorexic challenges. Complementary chemogenetic approaches were used in MC3R-Cre mice to localize and characterize the specific medial hypothalamic brain regions mediating the role of MC3R in energy homeostasis. Finally, we performed RNAscope in situ hybridization to map changes in the mRNA expression of MC3R, pro-opiomelanocortin and agouti-related peptide following energy rheostatic challenges, as well as to characterize the MC3R expressing cells in dorsal MH. Our results demonstrate that MC3R deletion in MH increases feeding and weight gain following high-fat diet feeding, and enhances the anorexic effects of semaglutide, in a sexually dimorphic manner. Furthermore, although the arcuate nucleus exerts an important role in MC3R-mediated effects on energy homeostasis, viral deletion in the dorsal MH also resulted in altered energy rheostasis, indicating that brain regions outside of the arcuate nucleus also contribute to the role of MC3R in energy rheostasis. Together, these results demonstrate that MC3R-mediated effects on energy rheostasis result from the loss of MC3R signalling in medial hypothalamic neurons and suggest an important role for dorsal-MH MC3R signalling in energy rheostasis. KEY POINTS: Melanocortin-3-receptor (MC3R) signalling regulates energy rheostasis in adult mice. Medial hypothalamus regulates energy rheostasis in adult mice. Energy rheostatic stimuli alter mRNA levels of agouti-related peptide, pro-opiomelanocortin and MC3R. Dorsal-medial hypothalamus (DMH) MC3R neurons increase locomotion and energy expenditure. MC3R cell types in DMH are sexually dimorphic.

  PublisherOA PDFDOI

• AB178. SOH24AB_224. A closed-loop audit of adherence to the sepsis management guidelines among adult patients suspected of sepsis presenting to the emergency department at Cork University Hospital

  Mesentery and Peritoneum · 2024-05-01

  articleOpen access1st authorCorresponding

  Background: Sepsis is defined as a dysregulated immune response to infection, leading to life-threatening organ dysfunction. It is a common, time-sensitive medical emergency, where positive outcomes depend on early recognition and intervention. Surviving sepsis campaign has set out guidelines for the management of sepsis which includes the Sepsis 6 treatment bundle. We measured adherence to the Health Service Executive (HSE) Clinical Guideline No. 6: sepsis resuscitation and management bundle tasks (Sepsis 6) by way of a closed-loop audit.

  PublisherDOI

• Hypothalamic AgRP neurons regulate the hyperphagia of lactation

  Molecular Metabolism · 2024-06-24 · 5 citations

  articleOpen accessSenior authorCorresponding

  OBJECTIVE: The lactational period is associated with profound hyperphagia to accommodate the energy demands of nursing. These changes are important for the long-term metabolic health of the mother and children as altered feeding during lactation increases the risk of mothers and offspring developing metabolic disorders later in life. However, the specific behavioral mechanisms and neural circuitry mediating the hyperphagia of lactation are incompletely understood. METHODS: Here, we utilized home cage feeding devices to characterize the dynamics of feeding behavior in lactating mice. A combination of pharmacological and behavioral assays were utilized to determine how lactation alters meal structure, circadian aspects of feeding, hedonic feeding, and sensitivity to hunger and satiety signals in lactating mice. Finally, we utilized chemogenetic, immunohistochemical, and in vivo imaging approaches to characterize the role of hypothalamic agouti-related peptide (AgRP) neurons in lactational-hyperphagia. RESULTS: The lactational period is associated with increased meal size, altered circadian patterns of feeding, reduced sensitivity to gut-brain satiety signals, and enhanced sensitivity to negative energy balance. Hypothalamic AgRP neurons display increased sensitivity to negative energy balance and altered in vivo activity during the lactational state. Further, using in vivo imaging approaches we demonstrate that AgRP neurons are directly activated by lactation. Chemogenetic inhibition of AgRP neurons acutely reduces feeding in lactating mice, demonstrating an important role for these neurons in lactational-hyperphagia. CONCLUSIONS: Together, these results show that lactation collectively alters multiple components of feeding behavior and position AgRP neurons as an important cellular substrate mediating the hyperphagia of lactation.

  PublisherDOI

• Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice

  Journal of Clinical Investigation · 2024-07-14 · 10 citations

  articleOpen access

  The melanocortin-3 receptor (MC3R) regulates GABA release from agouti-related protein (AgRP) nerve terminals and thus tonically suppresses multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of the MC3R and the melanocortin system in regulating the response to various anorexigenic agents. The genetic deletion or pharmacological inhibition of the MC3R, or subthreshold doses of an MC4R agonist, improved the dose responsiveness to glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor leptin demonstrated that increased sensitivity to anorectic agents was a generalized result of MC3R antagonism. We observed enhanced neuronal activation in multiple hypothalamic nuclei using Fos IHC following low-dose liraglutide in MC3R-KO mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits that control multiple aspects of feeding behavior. The enhanced anorectic response in Mc3r-/- mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1 receptor (GLP1R) analogs, suggesting that MC3R antagonists or MC4R agonists may have value in enhancing the dose-response range of obesity therapeutics.

  PublisherOA PDFDOI

Frequent coauthors

• Roger D. Cone

  University of Michigan–Ann Arbor

  18 shared

• Işın Çakır

  University of Michigan–Ann Arbor

  6 shared

• Anwar Ahmed

  6 shared

• Scott E. Cooper

  University of Minnesota

  6 shared

• William F. Hartsell

  6 shared

• Michal Gostkowski

  Cleveland Clinic

  6 shared

• Yunlei Yang

  SUNY Upstate Medical University

  6 shared

• Hubert H. Fernandez

  Dartmouth College

  6 shared

Labs

• Sweeney LabPI

Education

• Ph.D., Neuroscience

  SUNY Upstate Medical University

  2017