Cortical/hippocampal monoamines, HPA-axis changes and aversive behavior following stress and restress in an animal model of post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is characterized by monoaminergic and hypothalamic-pituitary-adrenal (HPA)-axis abnormalities. Understanding monoamine-HPA-axis responses following stress and restress may provide a greater understanding of the neurobiology of PTSD and of its treatment. Hippocampal and frontal cortex serotonin, noradrenaline and dopamine, plasma corticosterone and aversive behavior were studied in rats on day 1 and day 7 post acute stress (AS = sequential restraint stress, swim stress and halothane exposure), and on day 1 and day 7 post restress (RS = swim stress). After AS, there was an early increase in both avoidant behavior and corticosterone (1 h after stress), with subsequent normalisation (day 7), suggesting an adequate adaptive response to the stressor. However, restress (RS) evoked a significant early HPA-axis hyporesponsiveness (1 h after RS) and a later significant increase in avoidant behavior on day 7 post RS. Hippocampal serotonin, noradrenaline and dopamine concentrations were unchanged 1 h post AS, but were significantly raised on day 7 post AS. Restress, however, reduced serotonin and noradrenaline levels 1 h after and on day 7 post RS, respectively, while dopamine was unchanged. In the frontal cortex only dopamine levels were altered, being significantly elevated 1 h after AS, and reduced on day 7 post RS. AS and RS thus differently effect the HPA-axis, evoking regional-specific brain monoamine changes that underlie maladaptive behavior and other post stress-related sequelae.
Division of Pharmacology, School of Pharmacy, North-West University, Potchefstroom, 2520, South Africa. fklbhh@puk.ac.za
Brian H
BH
Harvey
Linda
L
Brand
Zakkiyya
Z
Jeeva
Dan J
DJ
Stein
D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000502:physiology*; D001522:Behavior, Animal; D015306:Biogenic Monoamines / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004195:Disease Models, Animal; D006624:Hippocampus / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D008297:Male; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012149:Restraint, Physical / Q000379:methods; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D013312:Stress, Physiological / Q000378:metabolism; D013997:Time Factors
D015306:Biogenic Monoamines