{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T03:22:48Z","timestamp":1788232968658,"version":"build-2803163510"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2011,10,12]],"date-time":"2011-10-12T00:00:00Z","timestamp":1318377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J intellect Disabil Res"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background\u2003<\/jats:bold> Self\u2010injurious behaviour (SIB) is prevalent in neurodevelopmental disorders, but its expression is highly variable within, and between diagnostic categories. This raises questions about the factors that contribute to aetiology and expression of SIB. Expression of SIB is generally described in relation to social reinforcement. However, variables that predispose vulnerability have not been as clearly characterised. This study reports the aetiology and expression of self\u2010injury in an animal model of pemoline\u2010induced SIB. It describes changes in gross neuronal activity in selected brain regions after chronic treatment with pemoline, and it describes the impact that a history of social defeat stress has on the subsequent expression of SIB during pemoline treatment.<\/jats:p><jats:p><jats:bold>Methods\u2003<\/jats:bold>  <jats:italic>Experiment 1<\/jats:italic>\u2013 Male Long\u2010Evans rats were injected on each of five consecutive days with pemoline or vehicle, and the expression of SIB was evaluated using a rating scale. The brains were harvested on the morning of the sixth day, and were assayed for expression of cytochrome oxidase, an index of sustained neuronal metabolic activity. <jats:italic>Experiment 2<\/jats:italic>\u2013 Male Long\u2010Evans rats were exposed to a regimen of 12 daily sessions of social defeat stress or 12 daily sessions of handling (i.e. controls). Starting on the day after completion of the social defeat or handling regimen, each rat was given five daily injections of pemoline. The durations of self\u2010injurious oral contact and other stereotyped behaviours were monitored, and the areas of tissue injury were quantified.<\/jats:p><jats:p><jats:bold>Results\u2003<\/jats:bold>  <jats:italic>Experiment 1<\/jats:italic>\u2013 Neuronal metabolic activity was significantly lower in a variety of limbic and limbic\u2010associated brain structures in the pemoline\u2010treated rats, when compared with activity in the same regions of vehicle\u2010treated controls. In addition, neuronal activity was low in the caudate\u2013putamen, and in subfields of the hypothalamus, but did not differ between groups for a variety of other brain regions, including nucleus accumbens, substantia nigra, ventral tegmentum, thalamus, amygdala, and cortical regions. <jats:italic>Experiment 2<\/jats:italic>\u2013 All the pemoline\u2010treated rats exhibited SIB, and whereas the social defeat regimen did not alter the total amount of self\u2010injurious oral contact or other stereotyped behaviours, it significantly increased the severity of tissue injury.<\/jats:p><jats:p><jats:bold>Conclusions\u2003<\/jats:bold> A broad sampling of regional metabolic activity indicates that the pemoline regimen produces enduring changes that are localised to specific limbic, hypothalamic and striatal structures. The potential role of limbic function in aetiology of SIB is further supported by the finding that pemoline\u2010induced self\u2010injury is exacerbated by prior exposure to social defeat stress. Overall, the results suggest brain targets that should be investigated further, and increase our understanding of the putative role that stress plays in the pathophysiology of SIB.<\/jats:p>","DOI":"10.1111\/j.1365-2788.2011.01485.x","type":"journal-article","created":{"date-parts":[[2011,10,12]],"date-time":"2011-10-12T10:57:28Z","timestamp":1318417048000},"page":"490-500","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Self\u2010injurious behaviour: limbic dysregulation and stress effects in an animal model"],"prefix":"10.1111","volume":"56","author":[{"given":"A. M.","family":"Muehlmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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