title: Endocrine, cognitive and hippocampal/cortical 5HT 1A/2A receptor changes evoked by a time-dependent sensitisation (TDS) stress model in rats.
abstract: Post traumatic stress disorder (PTSD) is characterised by hyperarousal, anxiety and amnesic symptoms. Deficits in explicit memory recall have been causally related to volume reductions of the hippocampus and prefrontal cortex. While stress-related glucocorticoid secretion appears involved in this apparent atrophy, there is also evidence for low plasma cortisol in PTSD. Prior exposure to trauma is an important risk factor for PTSD, suggesting a role for sensitisation. Using Sprague-Dawley rats, we studied the effects of a time-dependent sensitisation (TDS) model of stress on spatial memory deficits, 1 week post-stress, using the Morris water maze. Basal and 7-day post-stress plasma corticosterone levels were also determined. Due to the putative role of serotonin in anxiety and stress, and in the treatment of PTSD, hippocampal 5HT(1A) and prefrontal cortex 5HT(2A) radioligand binding studies were performed. TDS stress evoked a marked deficit in spatial memory on day 7 post TDS stress, coupled with significantly depressed plasma corticosterone levels. Cognitive and endocrine changes at day 7 post stress were associated with a significant increase in receptor density (B(max)) and a significant decrease in receptor affinity (K(d)) for hippocampal 5HT(1A) receptors. The B(max) of prefrontal cortex 5HT(2A) receptors were unaffected, but K(d) was significantly increased. We conclude that TDS stress evokes cognitive and endocrine changes characteristic of PTSD. Moreover, TDS stress induces diverse adaptive 5HT receptor changes in critical brain areas involved in emotion and memory that may underlie the effect of stress on cognitive function.
authors.affiliation: Division of Pharmacology, School of Pharmacy, Potchefstroom University for Christian Higher Education, 2520, Potchefstroom, South Africa. fklbhh@puknet.puk.ac.za
authors.forename: Brian H
authors.initials: BH
authors.lastname: Harvey
authors.forename: Carla
authors.initials: C
authors.lastname: Naciti
authors.forename: Linda
authors.initials: L
authors.lastname: Brand
authors.forename: Dan J
authors.initials: DJ
authors.lastname: Stein
mesh_terms: D000818:Animals; D001007:Anxiety / Q000523:psychology; D001143:Arousal / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D003345:Corticosterone / Q000097:blood; D003463:Cues; D004702:Endocrine Glands / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D007202:Indicators and Reagents; D008297:Male; D008568:Memory / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D044402:Receptor, Serotonin, 5-HT2A / Q000502:physiology*; D013028:Space Perception / Q000502:physiology; D013313:Stress Disorders, Post-Traumatic / Q000523:psychology; D013315:Stress, Psychological / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D007202:Indicators and Reagents; D044402:Receptor, Serotonin, 5-HT2A; D044282:Receptor, Serotonin, 5-HT1A; D003345:Corticosterone