{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T09:12:21Z","timestamp":1773393141671,"version":"3.50.1"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T00:00:00Z","timestamp":1750982400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000025","name":"National Institute of Mental Health","doi-asserted-by":"publisher","award":["R01MH053851"],"award-info":[{"award-number":["R01MH053851"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Motor impulsivity is a symptom shared by several psychiatric disorders. Stress exacerbates impulsivity, but the neurocircuits involved are unknown. We have shown that the orbitofrontal cortex (OFC) is activated during a rodent motor impulsivity task and that chronic unpredictable stress (CUS) increases premature responding. In this study, we examine the role of the OFC projection to dorsal medial striatum (DMS) in motor control, and test whether this pathway mediates the effects of stress on impulsive action.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Motor impulsivity was measured with the 1-choice serial reaction time test (1-CSRTT). To determine if OFC-DMS projections are involved in controlling impulsivity, we used pathway-specific Designer Receptors Exclusively Activated by Designer Drugs (DREADD)-mediated chemogenetic manipulation during 1-CSRTT. We examined stress effects on OFC-DMS neuronal activation using Fos immunohistochemistry. To assess if stress increases impulsivity through OFC-DMS projections, we chemogenetically manipulated the pathway in stressed rats during behavior.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We found OFC-DMS projections inhibit premature responding in a well-mastered task. Stress attenuated OFC neuronal activation, including the OFC-DMS projection neurons, during behavior. However, selectively activating the projection in stressed rats was not sufficient to abolish the stress effects. Finally, the response to stress depended on baseline trait impulsivity. Rats with low trait impulsivity were more vulnerable to stress and showed attenuated activation of OFC-DMS neurons but increased activation of other OFC cell populations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These results suggest the OFC-DMS pathway modulates impulsivity in concert with other OFC neuronal populations. Furthermore, stress effects are baseline-dependent and affect only low-impulsivity rats, possibly by altering the balance of activation in functionally opposing neuronal populations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/ijnp\/pyaf043","type":"journal-article","created":{"date-parts":[[2025,6,26]],"date-time":"2025-06-26T07:54:01Z","timestamp":1750924441000},"source":"Crossref","is-referenced-by-count":0,"title":["Involvement of a stress-responsive orbito-striatal projection in impulsive action in male rats"],"prefix":"10.1093","volume":"28","author":[{"given":"Milena","family":"Girotti","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio , San Antonio, TX ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maisie G","family":"Boehmer-Cortez","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio , San Antonio, TX ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7681-1158","authenticated-orcid":false,"given":"Kathleen","family":"Tuite","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio , San Antonio, TX ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6689-6258","authenticated-orcid":false,"given":"David A","family":"Morilak","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center at San Antonio , San Antonio, TX ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,6,27]]},"reference":[{"key":"2026031303421282200_ref1","volume-title":"The Impulsive Client; Theory, Research and Treatment","author":"Durana","year":"1993"},{"key":"2026031303421282200_ref2","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/7854_2015_393","article-title":"Skewed by cues? The motivational role of audiovisual stimuli in modelling substance use and gambling disorders","volume":"27","author":"Barrus","year":"2016","journal-title":"Curr Top Behav Neurosci"},{"key":"2026031303421282200_ref3","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1016\/j.neuron.2011.01.020","article-title":"Impulsivity, compulsivity, and top-down cognitive control","volume":"69","author":"Dalley","year":"2011","journal-title":"Neuron"},{"key":"2026031303421282200_ref4","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.neubiorev.2009.07.003","article-title":"Is there an inhibitory-response-control system in the rat? Evidence from anatomical and pharmacological studies of behavioral inhibition","volume":"34","author":"Eagle","year":"2010","journal-title":"Neurosci Biobehav Rev"},{"key":"2026031303421282200_ref5","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1007\/PL00005481","article-title":"Varieties of impulsivity","volume":"146","author":"Evenden","year":"1999","journal-title":"Psychopharmacology"},{"key":"2026031303421282200_ref6","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1037\/bne0000412","article-title":"The ever-changing OFC landscape: what neural signals in OFC can tell us about inhibitory control","volume":"135","author":"Brockett","year":"2021","journal-title":"Behav Neurosci"},{"key":"2026031303421282200_ref7","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1016\/j.bbr.2003.09.020","article-title":"Dissociable aspects of performance on the 5-choice serial reaction time task following lesions of the dorsal anterior cingulate, infralimbic and orbitofrontal cortex in the rat: differential effects on selectivity, impulsivity and compulsivity","volume":"146","author":"Chudasama","year":"2003","journal-title":"Behav Brain Res"},{"key":"2026031303421282200_ref8","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1037\/0735-7044.115.4.799","article-title":"Lesions of the medial and lateral striatum in the rat produce differential deficits in attentional performance","volume":"115","author":"Rogers","year":"2001","journal-title":"Behav Neurosci"},{"key":"2026031303421282200_ref9","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1002\/cne.20738","article-title":"Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers","volume":"492","author":"Gabbott","year":"2005","journal-title":"J Comp Neurol"},{"key":"2026031303421282200_ref10","doi-asserted-by":"crossref","first-page":"3766","DOI":"10.1002\/cne.22733","article-title":"Projections of the medial orbital and ventral orbital cortex in the rat","volume":"519","author":"Hoover","year":"2011","journal-title":"J Comp Neurol"},{"key":"2026031303421282200_ref11","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nprot.2008.41","article-title":"The application of the 5-choice serial reaction time task for the assessment of visual attentional processes and impulse control in rats","volume":"3","author":"Bari","year":"2008","journal-title":"Nat Protoc"},{"key":"2026031303421282200_ref12","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1097\/FBP.0b013e328345f90d","article-title":"Serotonin (5-hydroxytryptamine) 5-HT(2A) receptor: association with inherent and cocaine-evoked behavioral disinhibition in rats","volume":"22","author":"Anastasio","year":"2011","journal-title":"Behav Pharmacol"},{"key":"2026031303421282200_ref13","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1016\/S0893-133X(01)00412-2","article-title":"Deficits in impulse control associated with tonically-elevated serotonergic function in rat prefrontal cortex","volume":"26","author":"Dalley","year":"2002","journal-title":"Neuropsychopharmacology"},{"key":"2026031303421282200_ref14","doi-asserted-by":"crossref","first-page":"1752","DOI":"10.1038\/s41386-019-0394-8","article-title":"Convergent neural connectivity in motor impulsivity and high-fat food binge-like eating in male Sprague-Dawley rats","volume":"44","author":"Anastasio","year":"2019","journal-title":"Neuropsychopharmacology"},{"key":"2026031303421282200_ref15","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.neuroscience.2020.03.045","article-title":"Inherent motor impulsivity associates with specific gene targets in the rat medial prefrontal cortex","volume":"435","author":"Sholler","year":"2020","journal-title":"Neuroscience."},{"key":"2026031303421282200_ref16","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1124\/jpet.118.251199","article-title":"The 5-HT2A receptor (5-HT2AR) regulates impulsive action and cocaine cue reactivity in male Sprague-Dawley rats","volume":"368","author":"Sholler","year":"2019","journal-title":"J Pharmacol Exp Ther"},{"key":"2026031303421282200_ref17","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1177\/0269881114560182","article-title":"A comparison of impulsivity, depressive symptoms, lifetime stress and sensation seeking in healthy controls versus participants with cocaine or methamphetamine use disorders","volume":"29","author":"Mahoney","year":"2015","journal-title":"J Psychopharmacol"},{"key":"2026031303421282200_ref18","doi-asserted-by":"publisher","first-page":"2921","DOI":"10.1177\/1359105320937055","article-title":"Cumulative lifetime stress exposure predicts greater impulsivity and addictive behaviors","volume":"26","author":"McMullin","year":"2021","journal-title":"J Health Psychol"},{"key":"2026031303421282200_ref19","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1037\/bul0000060","article-title":"Effects of stress on decisions under uncertainty: a meta-analysis","volume":"142","author":"Starcke","year":"2016","journal-title":"Psychol Bull"},{"key":"2026031303421282200_ref20","doi-asserted-by":"crossref","first-page":"10668","DOI":"10.1038\/s41598-017-10745-9","article-title":"Impulsivity influences betting under stress in laboratory gambling","volume":"7","author":"Canale","year":"2017","journal-title":"Sci Rep"},{"key":"2026031303421282200_ref21","doi-asserted-by":"crossref","first-page":"7754","DOI":"10.1038\/s41598-020-64540-0","article-title":"Trait impulsivity and acute stress interact to influence choice and decision speed during multi-stage decision-making","volume":"10","author":"Raio","year":"2020","journal-title":"Sci Rep"},{"key":"2026031303421282200_ref22","doi-asserted-by":"crossref","first-page":"113488","DOI":"10.1016\/j.bbr.2021.113488","article-title":"Juvenile stress increases cocaine-induced impulsivity in female rats","volume":"414","author":"Paine","year":"2021","journal-title":"Behav Brain Res"},{"key":"2026031303421282200_ref23","doi-asserted-by":"crossref","first-page":"104638","DOI":"10.1016\/j.neubiorev.2022.104638","article-title":"The effects of early life stress on impulsivity","volume":"137","author":"Sanchez","year":"2022","journal-title":"Neurosci Biobehav Rev"},{"key":"2026031303421282200_ref24","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1093\/ijnp\/pyac062","article-title":"Role of orbitofrontal cortex and differential effects of acute and chronic stress on motor impulsivity measured with 1-choice serial reaction time test in male rats","volume":"25","author":"Girotti","year":"2022","journal-title":"Int J Neuropsychopharmacol"},{"key":"2026031303421282200_ref25","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1007\/s00213-015-3957-3","article-title":"Antidepressant-like cognitive and behavioral effects of acute ketamine administration associated with plasticity in the ventral hippocampus to medial prefrontal cortex pathway","volume":"232","author":"Jett","year":"2015","journal-title":"Psychopharmacology"},{"key":"2026031303421282200_ref26","doi-asserted-by":"publisher","first-page":"913","DOI":"10.1016\/j.pnpbp.2010.04.016","article-title":"Beneficial effects of desipramine on cognitive function of chronically stressed rats are mediated by alpha1-adrenergic receptors in medial prefrontal cortex","volume":"34","author":"Bondi","year":"2010","journal-title":"Prog Neuro-Psychopharmacol Biol Psychiatry"},{"key":"2026031303421282200_ref27","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1038\/sj.npp.1301410","article-title":"Chronic unpredictable stress induces a cognitive deficit and anxiety-like behavior in rats that is prevented by chronic antidepressant drug treatment","volume":"33","author":"Bondi","year":"2008","journal-title":"Neuropsychopharmacology"},{"key":"2026031303421282200_ref28","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1038\/npp.2012.216","article-title":"Too much of a good thing: blocking noradrenergic facilitation in medial prefrontal cortex prevents the detrimental effects of chronic stress on cognition","volume":"38","author":"Jett","year":"2013","journal-title":"Neuropsychopharmacology"},{"key":"2026031303421282200_ref29","doi-asserted-by":"crossref","first-page":"1593","DOI":"10.1073\/pnas.0508901103","article-title":"Leptin: a potential novel antidepressant","volume":"103","author":"Lu","year":"2006","journal-title":"Proc Natl Acad Sci USA"},{"key":"2026031303421282200_ref30","doi-asserted-by":"crossref","first-page":"3092","DOI":"10.1038\/npp.2016.127","article-title":"Therapeutic effects of extinction learning as a model of exposure therapy in rats","volume":"41","author":"Fucich","year":"2016","journal-title":"Neuropsychopharmacology"},{"key":"2026031303421282200_ref31","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1523\/JNEUROSCI.0635-17.2017","article-title":"Activity in the ventral medial prefrontal cortex is necessary for the therapeutic effects of extinction in rats","volume":"38","author":"Fucich","year":"2018","journal-title":"J Neurosci"},{"key":"2026031303421282200_ref32","doi-asserted-by":"crossref","DOI":"10.1038\/s41380-025-03380-8","article-title":"Antidepressant-like effects of extinction learning as an animal model of behavioral therapy","author":"Liu","year":"2025","journal-title":"Mol Psychiatry"},{"key":"2026031303421282200_ref33","volume-title":"The Rat Brain in Stereotaxic Coordinates","author":"Paxinos","year":"1997","edition":"3rd"},{"key":"2026031303421282200_ref34","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1126\/science.1137073","article-title":"Nucleus accumbens D2\/3 receptors predict trait impulsivity and cocaine reinforcement","volume":"315","author":"Dalley","year":"2007","journal-title":"Science"},{"key":"2026031303421282200_ref35","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1097\/00001756-200205070-00030","article-title":"Orbitofrontal lesions in rats impair reversal but not acquisition of go, no-go odor discriminations","volume":"13","author":"Schoenbaum","year":"2002","journal-title":"Neuroreport."},{"key":"2026031303421282200_ref36","doi-asserted-by":"crossref","first-page":"620","DOI":"10.1038\/nn.3982","article-title":"What the orbitofrontal cortex does not do","volume":"18","author":"Stalnaker","year":"2015","journal-title":"Nat Neurosci"},{"key":"2026031303421282200_ref37","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0015-24.2024","article-title":"Optogenetic inhibition of the orbitofrontal cortex disrupts inhibitory control during stop-change performance in male rats","volume":"11","author":"Brockett","year":"2024","journal-title":"eNeuro"},{"key":"2026031303421282200_ref38","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.neuron.2013.11.005","article-title":"Orbitofrontal cortex as a cognitive map of task space","volume":"81","author":"Wilson","year":"2014","journal-title":"Neuron"},{"key":"2026031303421282200_ref39","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1016\/j.neuron.2018.06.038","article-title":"Economic choice as an untangling of options into actions","volume":"99","author":"Yoo","year":"2018","journal-title":"Neuron."},{"key":"2026031303421282200_ref40","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1038\/npp.2013.199","article-title":"Functional status of the serotonin 5-HT2C receptor (5-HT2CR) drives interlocked phenotypes that precipitate relapse-like behaviors in cocaine dependence","volume":"39","author":"Anastasio","year":"2014","journal-title":"Neuropsychopharmacology"},{"key":"2026031303421282200_ref41","doi-asserted-by":"publisher","first-page":"52","DOI":"10.3389\/fnbeh.2017.00052","article-title":"Deep brain stimulation of the nucleus accumbens core affects trait impulsivity in a baseline-dependent manner","volume":"11","author":"Schippers","year":"2017","journal-title":"Front Behav Neurosci"},{"key":"2026031303421282200_ref42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00213-015-4148-y","article-title":"Does impulsivity change rate dependently following stimulant administration? A translational selective review and re-analysis","volume":"233","author":"Bickel","year":"2016","journal-title":"Psychopharmacology"},{"key":"2026031303421282200_ref43","doi-asserted-by":"publisher","DOI":"10.1523\/ENEURO.0408-24.2025","article-title":"Cocaine self-administration increases impulsive decision-making in low-impulsive rats associated with impaired functional connectivity in the mesocorticolimbic system","volume":"12","author":"Shen","year":"2025","journal-title":"eNeuro"},{"key":"2026031303421282200_ref44","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3389\/fnint.2012.00069","article-title":"Response inhibition signals and miscoding of direction in dorsomedial striatum","volume":"6","author":"Bryden","year":"2012","journal-title":"Front Integr Neurosci"},{"key":"2026031303421282200_ref45","doi-asserted-by":"crossref","first-page":"3903","DOI":"10.1523\/JNEUROSCI.3587-14.2015","article-title":"Executive control signals in orbitofrontal cortex during response inhibition","volume":"35","author":"Bryden","year":"2015","journal-title":"J Neurosci"},{"key":"2026031303421282200_ref46","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1016\/j.biopsych.2021.08.018","article-title":"Corticostriatal activity driving compulsive reward seeking","volume":"90","author":"Harada","year":"2021","journal-title":"Biol Psychiatry"},{"key":"2026031303421282200_ref47","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.brainresbull.2011.04.002","article-title":"Bilateral striatal lesions disrupt performance in an operant delayed reinforcement task in rats","volume":"88","author":"Dunnett","year":"2012","journal-title":"Brain Res Bull"},{"key":"2026031303421282200_ref48","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.biopsych.2013.07.013","article-title":"Gamma aminobutyric acidergic and neuronal structural markers in the nucleus accumbens core underlie trait-like impulsive behavior","volume":"75","author":"Caprioli","year":"2014","journal-title":"Biol Psychiatry"},{"key":"2026031303421282200_ref49","doi-asserted-by":"crossref","first-page":"112941","DOI":"10.1016\/j.bbr.2020.112941","article-title":"Kindling of the basolateral or central nucleus of the amygdala increases suboptimal choice in a rat gambling task and increases motor impulsivity in risk-preferring animals","volume":"398","author":"Tremblay","year":"2021","journal-title":"Behav Brain Res"},{"key":"2026031303421282200_ref50","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1038\/s41583-018-0039-7","article-title":"Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man","volume":"19","author":"Fenster","year":"2018","journal-title":"Nat Rev Neurosci"},{"key":"2026031303421282200_ref51","doi-asserted-by":"crossref","first-page":"100258","DOI":"10.1016\/j.ynstr.2020.100258","article-title":"Optogenetically-induced long term depression in the rat orbitofrontal cortex ameliorates stress-induced reversal learning impairment","volume":"13","author":"Adler","year":"2020","journal-title":"Neurobiol Stress"},{"key":"2026031303421282200_ref52","doi-asserted-by":"crossref","first-page":"744147","DOI":"10.3389\/fnint.2021.744147","article-title":"Editorial: advances in understanding of the functions of the paraventricular thalamic nucleus","volume":"15","author":"Bhatnagar","year":"2021","journal-title":"Front Integr Neurosci"},{"key":"2026031303421282200_ref53","doi-asserted-by":"publisher","first-page":"73","DOI":"10.3389\/fnbeh.2014.00073","article-title":"Contributions of the paraventricular thalamic nucleus in the regulation of stress, motivation, and mood","volume":"8","author":"Hsu","year":"2014","journal-title":"Front Behav Neurosci"},{"key":"2026031303421282200_ref54","doi-asserted-by":"publisher","first-page":"215","DOI":"10.1007\/BF00227299","article-title":"Neuronal connections of orbital cortex in rats: topography of cortical and thalamic afferents","volume":"111","author":"Reep","year":"1996","journal-title":"Exp Brain Res"}],"container-title":["International Journal of Neuropsychopharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ijnp\/advance-article-pdf\/doi\/10.1093\/ijnp\/pyaf043\/63606830\/pyaf043.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/28\/7\/pyaf043\/63606830\/pyaf043.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ijnp\/article-pdf\/28\/7\/pyaf043\/63606830\/pyaf043.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:42:24Z","timestamp":1773387744000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ijnp\/article\/doi\/10.1093\/ijnp\/pyaf043\/8176598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,27]]},"references-count":54,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2025,7,23]]}},"URL":"https:\/\/doi.org\/10.1093\/ijnp\/pyaf043","relation":{},"ISSN":["1461-1457","1469-5111"],"issn-type":[{"value":"1461-1457","type":"print"},{"value":"1469-5111","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,7]]},"published":{"date-parts":[[2025,6,27]]},"article-number":"pyaf043"}}