title: Self-injurious behaviour: limbic dysregulation and stress effects in an animal model.
abstract: BACKGROUND
  Self-injurious 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-injury in an animal model of pemoline-induced 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.
  
  
  METHODS
  Experiment 1--Male Long-Evans 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. Experiment 2--Male Long-Evans 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-injurious oral contact and other stereotyped behaviours were monitored, and the areas of tissue injury were quantified.
  
  
  RESULTS
  Experiment 1--Neuronal metabolic activity was significantly lower in a variety of limbic and limbic-associated brain structures in the pemoline-treated rats, when compared with activity in the same regions of vehicle-treated controls. In addition, neuronal activity was low in the caudate-putamen, 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. Experiment 2--All the pemoline-treated rats exhibited SIB, and whereas the social defeat regimen did not alter the total amount of self-injurious oral contact or other stereotyped behaviours, it significantly increased the severity of tissue injury.
  
  
  CONCLUSIONS
  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-induced self-injury 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.
authors: Behavioral and Cognitive Neuroscience Program, Department of Psychology, University of Florida, Gainesville, Florida 32611-2250, USA.
authors: A M
authors: AM
authors: Muehlmann
authors: S D
authors: SD
authors: Kies
authors: C A
authors: CA
authors: Turner
authors: S
authors: S
authors: Wolfman
authors: M H
authors: MH
authors: Lewis
authors: D P
authors: DP
authors: Devine
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000503:physiopathology; D007926:Lesch-Nyhan Syndrome / Q000503:physiopathology*; D008032:Limbic System / Q000187:drug effects / Q000503:physiopathology*; D008297:Male; D010389:Pemoline / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D016728:Self-Injurious Behavior / Q000139:chemically induced / Q000503:physiopathology*; D012930:Social Dominance; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D000697:Central Nervous System Stimulants; D010389:Pemoline; D003576:Electron Transport Complex IV