Neural responses in rat brain during acute immobilization stress: A [F-18]FDG micro PET imaging study

We used the [F-18]FDG micro PET neuroimaging technique to investigate changes in brain activity induced by acute stress in rats. Animals were given immobilization stress for 1 or 2 h, or 1-h stress followed by 1-h recovery, after which their brains were scanned. Plasma corticosterone levels measured at various time points in separate groups of rats showed a rapid increase during stress and slower decrease after termination of the stress. Immobilization stress given for an hour activated the hypothalamus, entorhinal and insular/piriform cortices, and raphe pallidus nucleus. At the same time, the dorsal hippocampus, thalamus, other cortical areas (motor, somatosensory and barrel field), striatum, superior colliculus and cerebellum were deactivated. With 2-h immobilization stress, the activity of the hypothalamus, various cortical areas and dorsal hippocampus habituated during the second hour while that of the thalamus and cerebellum did not. During 1-h recovery, the hypothalamic activation and widespread cortical deactivation disappeared, but the dorsal hippocampus, thalamus and cerebellum still remained significantly deactivated. Additional brain areas such as the septum and prelimbic cortex now showed deactivation during recovery. Changes in glucose metabolism in the dorsal hippocampus and hypothalamus exhibited a highly significant negative correlation, supporting the view that the hippocampus is involved in regulating the stress response of the hypothalamo-pituitary-adrenal axis. The advantages and limitations of the [F-18]FDG micro PET used in this study are discussed.

[1]  Stella E Tsirka,et al.  PET imaging of glucose metabolism in a mouse model of temporal lobe epilepsy , 2006, Synapse.

[2]  I. Liberzon,et al.  Paralimbic and medial prefrontal cortical involvement in neuroendocrine responses to traumatic stimuli. , 2007, The American journal of psychiatry.

[3]  Jens C. Pruessner,et al.  Deactivation of the Limbic System During Acute Psychosocial Stress: Evidence from Positron Emission Tomography and Functional Magnetic Resonance Imaging Studies , 2008, Biological Psychiatry.

[4]  Kaoru Kobayashi,et al.  MicroPET detection of enhanced 18F-FDG utilization by PKA inhibitor in awake rat brain , 2005, Brain Research.

[5]  Jurgen Seidel,et al.  Measurement of cerebral glucose metabolic rates in the anesthetized rat by dynamic scanning with 18F-FDG, the ATLAS small animal PET scanner, and arterial blood sampling. , 2004, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[6]  Ahmad R. Hariri,et al.  Individual Differences in Stressor-Evoked Blood Pressure Reactivity Vary with Activation, Volume, and Functional Connectivity of the Amygdala , 2008, The Journal of Neuroscience.

[7]  J. Herman,et al.  Neurocircuitry of stress: central control of the hypothalamo–pituitary–adrenocortical axis , 1997, Trends in Neurosciences.

[8]  Anat Biegon,et al.  Serial microPET measures of the metabolic reaction to a microdialysis probe implant , 2006, Journal of Neuroscience Methods.

[9]  A. Armario,et al.  Recovery of the Hypothalamic-Pituitary-Adrenal Response to Stress , 2000, Neuroendocrinology.

[10]  R. Vrba Glucose Metabolism in Rat Brain In Vivo , 1962, Nature.

[11]  A. Lörincz,et al.  Physiological patterns in the hippocampo‐entorhinal cortex system , 2000, Hippocampus.

[12]  M. Raichle,et al.  Stimulus rate dependence of regional cerebral blood flow in human striate cortex, demonstrated by positron emission tomography. , 1984, Journal of neurophysiology.

[13]  S. Watson Neuroendocrine and Behavioral Responses and Brain Pattern of c‐fos Induction Associated with Audiogenic Stress , 1997, Journal of neuroendocrinology.

[14]  S. Watson,et al.  Fos expression in forebrain afferents to the hypothalamic paraventricular nucleus following swim stress , 1996, The Journal of comparative neurology.

[15]  A. Armario,et al.  Long-term effects of a single exposure to immobilization: a c-fos mRNA study of the response to the homotypic stressor in the rat brain. , 2006, Journal of neurobiology.

[16]  H. Umegaki,et al.  Involvement of the Entorhinal Cortex in the Stress Response to Immobilization, But Not to Insulin‐Induced Hypoglycaemia , 2003, Journal of neuroendocrinology.

[17]  M. Dallman,et al.  Corticosteroids and the Control of Function in the Hypothalamo‐Pituitary‐Adrenal (HPA) Axis a , 1994, Annals of the New York Academy of Sciences.

[18]  J. S. Lee,et al.  Performance Measurement of the microPET Focus 120 Scanner , 2007, Journal of Nuclear Medicine.

[19]  G. Koob,et al.  Stress: Neurobiology and Neuroendocrinology , 1990 .

[20]  R. Ahn,et al.  Spontaneous maturation of follicular oocytes in Rana dybowskii in vitro: seasonal influences, progesterone production and involvement of cAMP. , 1989, The Journal of experimental zoology.

[21]  Michael E Phelps,et al.  Impact of animal handling on the results of 18F-FDG PET studies in mice. , 2006, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[22]  Joanna S. Fowler,et al.  A novel approach for imaging brain–behavior relationships in mice reveals unexpected metabolic patterns during seizures in the absence of tissue plasminogen activator , 2007, NeuroImage.

[23]  H. Selye What is stress? , 1956, Metabolism: clinical and experimental.

[24]  H. Akil,et al.  Pattern and time course of immediate early gene expression in rat brain following acute stress , 1995, Neuroscience.

[25]  Jesper L. R. Andersson,et al.  A template for spatial normalisation of MR images of the rat brain , 2003, Journal of Neuroscience Methods.

[26]  D. Morilak,et al.  Induction of FOS expression by acute immobilization stress is reduced in locus coeruleus and medial amygdala of Wistar–Kyoto rats compared to Sprague–Dawley rats , 2004, Neuroscience.

[27]  K. Johnson,et al.  Topographic patterns of brain activity in response to swim stress: assessment by 2-deoxyglucose uptake and expression of Fos-like immunoreactivity , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.